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Sample records for underlie voltage-dependent calcium

  1. Voltage-dependent mobilization of intracellular calcium in skeletal muscle.

    Science.gov (United States)

    Schneider, M F

    1986-01-01

    In skeletal muscle calcium is released from the sarcoplasmic reticulum (SR), an internal organelle, in response to changes in the voltage across the transverse tubule (T-tubule) membrane, an external membrane system that is distinct from the SR but in close proximity to it. For T-tubule voltage changes within the physiological range, calcium release can be turned on or off on a time scale of milliseconds. The control of calcium release from the SR appears to involve at least three functional components: a voltage sensor in the T-tubule membrane, a calcium channel in the SR, and a mechanism for coupling the voltage sensor to the channel. Movement of charged or dipolar molecules within the T-tubule membrane is thought to serve as the voltage sensor. Such intramembrane charge movement (Q) can be monitored electrically and can be compared with the rate of calcium release from the SR. Calcium release is calculated from cytosolic calcium transients measured with a metallochromic indicator. Comparison of Q and the rate of release in the same isolated muscle fibre indicates that this rate is directly proportional to the amount of charge displaced in excess of a 'threshold' amount. The nature of the coupling mechanism between T-tubules and SR remains to be established but present observations impose some restrictions on possible mechanisms.

  2. Localization and pharmacological characterization of voltage dependent calcium channels in cultured neocortical neurons

    DEFF Research Database (Denmark)

    Timmermann, D B; Lund, Trine Meldgaard; Belhage, B

    2001-01-01

    The physiological significance and subcellular distribution of voltage dependent calcium channels was defined using calcium channel blockers to inhibit potassium induced rises in cytosolic calcium concentration in cultured mouse neocortical neurons. The cytosolic calcium concentration was measured...... channels were differentially distributed in somata, neurites and nerve terminals. omega-conotoxin MVIIC (omega-CgTx MVIIC) inhibited approximately 40% of the Ca(2+)-rise in both somata and neurites and 60% of the potassium induced [3H]GABA release, indicating that the Q-type channel is the quantitatively...... using the fluorescent calcium chelator fura-2. The types of calcium channels present at the synaptic terminal were determined by the inhibitory action of calcium channel blockers on potassium-induced [3H]GABA release in the same cell preparation. L-, N-, P-, Q- and R-/T-type voltage dependent calcium...

  3. Calmodulin and calcium differentially regulate the neuronal Nav1.1 voltage-dependent sodium channel

    Energy Technology Data Exchange (ETDEWEB)

    Gaudioso, Christelle; Carlier, Edmond; Youssouf, Fahamoe [INSERM U641, Institut Jean Roche, Marseille F-13344 (France); Universite de la Mediterranee, Faculte de Medecine Secteur Nord, IFR 11, Marseille F-13344 (France); Clare, Jeffrey J. [Eaton Pharma Consulting, Eaton Socon, Cambridgeshire PE19 8EF (United Kingdom); Debanne, Dominique [INSERM U641, Institut Jean Roche, Marseille F-13344 (France); Universite de la Mediterranee, Faculte de Medecine Secteur Nord, IFR 11, Marseille F-13344 (France); Alcaraz, Gisele, E-mail: gisele.alcaraz@univmed.fr [INSERM U641, Institut Jean Roche, Marseille F-13344 (France); Universite de la Mediterranee, Faculte de Medecine Secteur Nord, IFR 11, Marseille F-13344 (France)

    2011-07-29

    Highlights: {yields} Both Ca{sup ++}-Calmodulin (CaM) and Ca{sup ++}-free CaM bind to the C-terminal region of Nav1.1. {yields} Ca{sup ++} and CaM have both opposite and convergent effects on I{sub Nav1.1}. {yields} Ca{sup ++}-CaM modulates I{sub Nav1.1} amplitude. {yields} CaM hyperpolarizes the voltage-dependence of activation, and increases the inactivation rate. {yields} Ca{sup ++} alone antagonizes CaM for both effects, and depolarizes the voltage-dependence of inactivation. -- Abstract: Mutations in the neuronal Nav1.1 voltage-gated sodium channel are responsible for mild to severe epileptic syndromes. The ubiquitous calcium sensor calmodulin (CaM) bound to rat brain Nav1.1 and to the human Nav1.1 channel expressed by a stably transfected HEK-293 cell line. The C-terminal region of the channel, as a fusion protein or in the yeast two-hybrid system, interacted with CaM via a consensus C-terminal motif, the IQ domain. Patch clamp experiments on HEK1.1 cells showed that CaM overexpression increased peak current in a calcium-dependent way. CaM had no effect on the voltage-dependence of fast inactivation, and accelerated the inactivation kinetics. Elevating Ca{sup ++} depolarized the voltage-dependence of fast inactivation and slowed down the fast inactivation kinetics, and for high concentrations this effect competed with the acceleration induced by CaM alone. Similarly, the depolarizing action of calcium antagonized the hyperpolarizing shift of the voltage-dependence of activation due to CaM overexpression. Fluorescence spectroscopy measurements suggested that Ca{sup ++} could bind the Nav1.1 C-terminal region with micromolar affinity.

  4. Pertussis toxin-sensitive alpha-adrenergic modulation of voltage - dependent calcium channels in spontaneously hypertensive rats (SHR)

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Pintérová, Mária; Dobešová, Zdenka; Líšková, Silvia; Kuneš, Jaroslav

    2006-01-01

    Roč. 24, č. S6 (2006), s. 34-34 ISSN 0263-6352. [Scientific Meeting of the International Society of Hypertension /21./. 15.10.2006-19.10.2006, Fukuoka] R&D Projects: GA MZd(CZ) NR7786 Institutional research plan: CEZ:AV0Z50110509 Keywords : pertussis toxin * alpha adrenergic vasoconstriction * voltage-dependent calcium channels * SHR rat Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  5. Voltage dependence of membrane charge movement and calcium release in frog skeletal muscle fibres.

    Science.gov (United States)

    Rakowski, R F; Best, P M; James-Kracke, M R

    1985-08-01

    Voltage dependent membrane charge movement (gating current) and the release of Ca2+ from intracellular stores have been measured simultaneously in intact frog skeletal muscle fibres. Charge movement was measured using the three microelectrode voltage clamp technique. Ca2+ release was measured using the metallochromic indicator dye arsenazo III. Fibres were bathed in 2.3 X hypertonic solutions to prevent contraction. Rb+, tetraethylammonium and tetrodotoxin (TTX) were used to eliminate voltage-dependent ionic currents. The maximum rate of Ca2+ release from the sarcoplasmic reticulum in response to voltage-clamp step depolarizations to 0 mV was calculated using the dye-related parameters of model 2 of Baylor et al. (1983) and a method described in the Appendix for calculating a scaling factor (1 + p) that accounts for the additional Ca2+ buffering power of the indicator dye. The estimates of the maximum rate of Ca2+ release at 5-6 degrees C ranged from 3 to 19 microM ms-1 in the 17 fibres examined. The mean value was 8.9 +/- 1.1 microM ms-1 (S.E.M.) The maximum rate of Ca2+ release was linearly related to the magnitude of the nonlinear membrane change moved during suprathreshold depolarizing steps. The voltage dependence of charge movement and the maximum rate of Ca2+ releases were nearly identical at 6 degrees C. The voltage-dependence of the delay between the test step and the onset of Ca2+ release could be adequately described by an equation having the same functional form as the voltage dependence of nonlinear charge movement. The relationship between the test pulse voltage and the delay was shifted to more negative voltages and to shorter delays as the temperature was raised from 6 degrees C to 15 degrees C. The inactivation of Ca2+ release was found to occur at more negative holding voltages and to be more steeply voltage dependent than the immobilization of nonlinear membrane charge movement. The above data are discussed using the 'hypothetical coupler' model

  6. Effects of captopril treatment on augmented norepinephrine-stimulated calcium entry through voltage-dependent calcium channels in spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Paulis, Ĺudovít; Dobešová, Zdenka; Kuneš, Jaroslav

    2006-01-01

    Roč. 24, č. S4 (2006), S338-S338 ISSN 0263-6352. [European Meeting on Hypertension /16./. 12.06.2006-15.06.2006, Madrid] R&D Projects: GA MZd(CZ) NR7786 Keywords : voltage-dependent calcium channel * hypertension * captopril * norepinephrine Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  7. Differential expression of T- and L-type voltage-dependent calcium channels in renal resistance vessels

    DEFF Research Database (Denmark)

    Hansen, Pernille B. Lærkegaard; Jensen, Boye L.; Andreasen, D

    2001-01-01

    The distribution of voltage-dependent calcium channels in kidney pre- and postglomerular resistance vessels was determined at the molecular and functional levels. Reverse transcription-polymerase chain reaction analysis of microdissected rat preglomerular vessels and cultured smooth muscle cells...... showed coexpression of mRNAs for T-type subunits (Ca(V)3.1, Ca(V)3.2) and for an L-type subunit (Ca(V)1.2). The same expression pattern was observed in juxtamedullary efferent arterioles and outer medullary vasa recta. No calcium channel messages were detected in cortical efferent arterioles. Ca(V)1.......2 protein was demonstrated by immunochemical labeling of rat preglomerular vasculature and juxtamedullary efferent arterioles and vasa recta. Cortical efferent arterioles were not immunopositive. Recordings of intracellular calcium concentration with digital fluorescence imaging microscopy showed...

  8. Calcium dysregulation via L-type voltage-dependent calcium channels and ryanodine receptors underlies memory deficits and synaptic dysfunction during chronic neuroinflammation.

    Science.gov (United States)

    Hopp, Sarah C; D'Angelo, Heather M; Royer, Sarah E; Kaercher, Roxanne M; Crockett, Alexis M; Adzovic, Linda; Wenk, Gary L

    2015-03-25

    Chronic neuroinflammation and calcium (Ca(+2)) dysregulation are both components of Alzheimer's disease. Prolonged neuroinflammation produces elevation of pro-inflammatory cytokines and reactive oxygen species which can alter neuronal Ca(+2) homeostasis via L-type voltage-dependent Ca(+2) channels (L-VDCCs) and ryanodine receptors (RyRs). Chronic neuroinflammation also leads to deficits in spatial memory, which may be related to Ca(+2) dysregulation. The studies herein use an in vivo model of chronic neuroinflammation: rats were infused intraventricularly with a continuous small dose of lipopolysaccharide (LPS) or artificial cerebrospinal fluid (aCSF) for 28 days. The rats were treated with the L-VDCC antagonist nimodipine or the RyR antagonist dantrolene. LPS-infused rats had significant memory deficits in the Morris water maze, and this deficit was ameliorated by treatment with nimodipine. Synaptosomes from LPS-infused rats had increased Ca(+2) uptake, which was reduced by a blockade of L-VDCCs either in vivo or ex vivo. Taken together, these data indicate that Ca(+2) dysregulation during chronic neuroinflammation is partially dependent on increases in L-VDCC function. However, blockade of the RyRs also slightly improved spatial memory of the LPS-infused rats, demonstrating that other Ca(+2) channels are dysregulated during chronic neuroinflammation. Ca(+2)-dependent immediate early gene expression was reduced in LPS-infused rats treated with dantrolene or nimodipine, indicating normalized synaptic function that may underlie improvements in spatial memory. Pro-inflammatory markers are also reduced in LPS-infused rats treated with either drug. Overall, these data suggest that Ca(+2) dysregulation via L-VDCCs and RyRs play a crucial role in memory deficits resulting from chronic neuroinflammation.

  9. Differential rescue of spatial memory deficits in aged rats by L-type voltage-dependent calcium channel and ryanodine receptor antagonism.

    Science.gov (United States)

    Hopp, S C; D'Angelo, H M; Royer, S E; Kaercher, R M; Adzovic, L; Wenk, G L

    2014-11-07

    Age-associated memory impairments may result as a consequence of neuroinflammatory induction of intracellular calcium (Ca(+2)) dysregulation. Altered L-type voltage-dependent calcium channel (L-VDCC) and ryanodine receptor (RyR) activity may underlie age-associated learning and memory impairments. Various neuroinflammatory markers are associated with increased activity of both L-VDCCs and RyRs, and increased neuroinflammation is associated with normal aging. In vitro, pharmacological blockade of L-VDCCs and RyRs has been shown to be anti-inflammatory. Here, we examined whether pharmacological blockade of L-VDCCs or RyRs with the drugs nimodipine and dantrolene, respectively, could improve spatial memory and reduce age-associated increases in microglia activation. Dantrolene and nimodipine differentially attenuated age-associated spatial memory deficits but were not anti-inflammatory in vivo. Furthermore, RyR gene expression was inversely correlated with spatial memory, highlighting the central role of Ca(+2) dysregulation in age-associated memory deficits. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart

    NARCIS (Netherlands)

    Schultz, D; Mikala, G; Yatani, A; Engle, D B; Iles, D E; Segers, B; Sinke, R J; Weghuis, D O; Klöckner, U; Wakamori, M

    1993-01-01

    A unique structural variant of the cardiac L-type voltage-dependent calcium channel alpha 1 subunit cDNA was isolated from libraries derived from normal human heart mRNA. The deduced amino acid sequence shows significant homology to other calcium channel alpha 1 subunits. However, differences from

  11. Impaired control of L-type voltage-dependent calcium channels in experimental hypertension

    Czech Academy of Sciences Publication Activity Database

    Pintérová, Mária; Líšková, Silvia; Dobešová, Zdenka; Behuliak, M.; Kuneš, Jaroslav; Zicha, Josef

    2009-01-01

    Roč. 58, Suppl.2 (2009), S43-S54 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/08/0139; GA ČR(CZ) GA305/09/0336; GA AV ČR(CZ) IAA500110902; GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : calcium-activated K+ and Cl- channels * vasoactive systems * EDCF Subject RIV: ED - Physiology Impact factor: 1.430, year: 2009

  12. VOLTAGE-DEPENDENT SODIUM AND POTASSIUM, BUT NO CALCIUM CONDUCTANCES IN DDT1 MF-2 SMOOTH-MUSCLE CELLS

    NARCIS (Netherlands)

    MOLLEMAN, A; NELEMANS, A; VANDENAKKER, J; DUIN, M; DENHERTOG, A

    Voltage-dependent inward and outward membrane currents were investigated in the DDT1 MF-2 smooth muscle cell line using the whole-cell patch-clamp technique. Application of a pulse protocol with subsequent depolarizing voltage steps elicited an inactivating inward current and a non-inactivating

  13. Developmental regulation of expression of the alpha 1 and alpha 2 subunits mRNAs of the voltage-dependent calcium channel in a differentiating myogenic cell line.

    Science.gov (United States)

    Varadi, G; Orlowski, J; Schwartz, A

    1989-07-03

    The voltage-dependent calcium channel (VDCC) in skeletal muscle probably plays a key role in transducing membrane charge movement to the calcium release channel. We report here that the expression of VDCC alpha 1 and alpha 2 mRNAs is developmentally regulated in differentiating C2C12 myogenic cells. The alpha 1 mRNA is not detectable in the myoblast form of C2C12 cells while its expression is induced 20-fold in differentiated myotubes. In contrast, the alpha 2 mRNA is weakly expressed in myoblasts but is also induced upon myogenic differentiation.

  14. Molecular and functional identification of cyclic AMP-sensitive BKCa potassium channels (ZERO variant) and L-type voltage-dependent calcium channels in single rat juxtaglomerular cells

    DEFF Research Database (Denmark)

    Friis, Ulla G; Jørgensen, Finn; Andreasen, Ditte

    2003-01-01

    This study aimed at identifying the type and functional significance of potassium channels and voltage-dependent calcium channels (Ca(v)) in single rat JG cells using whole-cell patch clamp. Single JG cells displayed outward rectification at positive membrane potentials and limited net currents......, respectively. Double immunofluorescence confirmed the presence of BKCa and renin in the same cell. cAMP increased the outward current by 1.6-fold, and this was inhibited by 74% with iberiotoxin. Expression of the cAMP-sensitive splice variant (ZERO) of BKCa was confirmed in single-sampled JG cells by RT...... no effect. We conclude that JG cells express functional cAMP-sensitive BKCa channels (the ZERO splice variant) and voltage-dependent L-type Ca2+ channels....

  15. Functional coupling between large-conductance potassium channels and Cav3.2 voltage-dependent calcium channels participates in prostate cancer cell growth

    Directory of Open Access Journals (Sweden)

    Florian Gackière

    2013-07-01

    It is strongly suspected that potassium (K+ channels are involved in various aspects of prostate cancer development, such as cell growth. However, the molecular nature of those K+ channels implicated in prostate cancer cell proliferation and the mechanisms through which they control proliferation are still unknown. This study uses pharmacological, biophysical and molecular approaches to show that the main voltage-dependent K+ current in prostate cancer LNCaP cells is carried by large-conductance BK channels. Indeed, most of the voltage-dependent current was inhibited by inhibitors of BK channels (paxillin and iberiotoxin and by siRNA targeting BK channels. In addition, we reveal that BK channels constitute the main K+ channel family involved in setting the resting membrane potential in LNCaP cells at around −40 mV. This consequently promotes a constitutive calcium entry through T-type Cav3.2 calcium channels. We demonstrate, using single-channel recording, confocal imaging and co-immunoprecipitation approaches, that both channels form macromolecular complexes. Finally, using flow cytometry cell cycle measurements, cell survival assays and Ki67 immunofluorescent staining, we show that both BK and Cav3.2 channels participate in the proliferation of prostate cancer cells.

  16. Ferulic Acid Suppresses Glutamate Release Through Inhibition of Voltage-Dependent Calcium Entry in Rat Cerebrocortical Nerve Terminals

    Science.gov (United States)

    Lin, Tzu Yu; Lu, Cheng Wei; Huang, Shu-Kuei

    2013-01-01

    Abstract This study investigated the effects and possible mechanism of ferulic acid, a naturally occurring phenolic compound, on endogenous glutamate release in the nerve terminals of the cerebral cortex in rats. Results show that ferulic acid inhibited the release of glutamate evoked by the K+ channel blocker 4-aminopyridine (4-AP). The effect of ferulic acid on the evoked glutamate release was prevented by chelating the extracellular Ca2+ ions, but was insensitive to the glutamate transporter inhibitor DL-threo-beta-benzyl-oxyaspartate. Ferulic acid suppressed the depolarization-induced increase in a cytosolic-free Ca2+ concentration, but did not alter 4-AP–mediated depolarization. Furthermore, the effect of ferulic acid on evoked glutamate release was abolished by blocking the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, but not by blocking ryanodine receptors or mitochondrial Na+/Ca2+ exchange. These results show that ferulic acid inhibits glutamate release from cortical synaptosomes in rats through the suppression of presynaptic voltage-dependent Ca2+ entry. PMID:23342970

  17. The Nitric Oxide Donor SNAP-Induced Amino Acid Neurotransmitter Release in Cortical Neurons. Effects of Blockers of Voltage-Dependent Sodium and Calcium Channels

    Science.gov (United States)

    Merino, José Joaquín; Arce, Carmen; Naddaf, Ahmad; Bellver-Landete, Victor; Oset-Gasque, Maria Jesús; González, María Pilar

    2014-01-01

    Background The discovery that nitric oxide (NO) functions as a signalling molecule in the nervous system has radically changed the concept of neuronal communication. NO induces the release of amino acid neurotransmitters but the underlying mechanisms remain to be elucidated. Findings The aim of this work was to study the effect of NO on amino acid neurotransmitter release (Asp, Glu, Gly and GABA) in cortical neurons as well as the mechanism underlying the release of these neurotransmitters. Cortical neurons were stimulated with SNAP, a NO donor, and the release of different amino acid neurotransmitters was measured by HPLC. The involvement of voltage dependent Na+ and Ca2+ channels as well as cGMP in its mechanism of action was evaluated. Conclusions Our results indicate that NO induces release of aspartate, glutamate, glycine and GABA in cortical neurons and that this release is inhibited by ODQ, an inhibitor of soluble guanylate cyclase. Thus, the NO effect on amino acid neurotransmission could be mediated by cGMP formation in cortical neurons. Our data also demonstrate that the Na+ and Ca2+ voltage- dependent calcium channels are involved in the NO effects on cortical neurons. PMID:24598811

  18. Dopamine Induces LTP Differentially in Apical and Basal Dendrites through BDNF and Voltage-Dependent Calcium Channels

    Science.gov (United States)

    Navakkode, Sheeja; Sajikumar, Sreedharan; Korte, Martin; Soong, Tuck Wah

    2012-01-01

    The dopaminergic modulation of long-term potentiation (LTP) has been studied well, but the mechanism by which dopamine induces LTP (DA-LTP) in CA1 pyramidal neurons is unknown. Here, we report that DA-LTP in basal dendrites is dependent while in apical dendrites it is independent of activation of L-type voltage-gated calcium channels (VDCC).…

  19. "Slow" Voltage-Dependent Inactivation of CaV2.2 Calcium Channels Is Modulated by the PKC Activator Phorbol 12-Myristate 13-Acetate (PMA.

    Directory of Open Access Journals (Sweden)

    Lei Zhu

    Full Text Available CaV2.2 (N-type voltage-gated calcium channels (Ca2+ channels play key roles in neurons and neuroendocrine cells including the control of cellular excitability, neurotransmitter / hormone secretion, and gene expression. Calcium entry is precisely controlled by channel gating properties including multiple forms of inactivation. "Fast" voltage-dependent inactivation is relatively well-characterized and occurs over the tens-to- hundreds of milliseconds timeframe. Superimposed on this is the molecularly distinct, but poorly understood process of "slow" voltage-dependent inactivation, which develops / recovers over seconds-to-minutes. Protein kinases can modulate "slow" inactivation of sodium channels, but little is known about if/how second messengers control "slow" inactivation of Ca2+ channels. We investigated this using recombinant CaV2.2 channels expressed in HEK293 cells and native CaV2 channels endogenously expressed in adrenal chromaffin cells. The PKC activator phorbol 12-myristate 13-acetate (PMA dramatically prolonged recovery from "slow" inactivation, but an inactive control (4α-PMA had no effect. This effect of PMA was prevented by calphostin C, which targets the C1-domain on PKC, but only partially reduced by inhibitors that target the catalytic domain of PKC. The subtype of the channel β-subunit altered the kinetics of inactivation but not the magnitude of slowing produced by PMA. Intracellular GDP-β-S reduced the effect of PMA suggesting a role for G proteins in modulating "slow" inactivation. We postulate that the kinetics of recovery from "slow" inactivation could provide a molecular memory of recent cellular activity and help control CaV2 channel availability, electrical excitability, and neurotransmission in the seconds-to-minutes timeframe.

  20. The effect of Cyclin-dependent kinase 5 on voltage-dependent calcium channels in PC12 cells varies according to channel type and cell differentiation state.

    Science.gov (United States)

    Furusawa, Kotaro; Asada, Akiko; Saito, Taro; Hisanaga, Shin-ichi

    2014-08-01

    Cyclin-dependent kinase 5 (Cdk5) is a Ser/Thr kinase that plays an important role in the release of neurotransmitter from pre-synaptic terminals triggered by Ca(2+) influx into the pre-synaptic cytoplasm through voltage-dependent Ca(2+) channels (VDCCs). It is reported that Cdk5 regulates L-, P/Q-, or N-type VDCC, but there is conflicting data as to the effect of Cdk5 on VDCC activity. To clarify the mechanisms involved, we examined the role of Cdk5 in regulating the Ca(2+) -channel property of VDCCs, using PC12 cells expressing endogenous, functional L-, P/Q-, and N-type VDCCs. The Ca(2+) influx, induced by membrane depolarization with high K(+) , was monitored with a fluorescent Ca(2+) indicator protein in both undifferentiated and nerve growth factor (NGF)-differentiated PC12 cells. Overall, Ca(2+) influx was increased by expression of Cdk5-p35 in undifferentiated PC12 cells but suppressed in differentiated PC12 cells. Moreover, we found that different VDCCs are distinctly regulated by Cdk5-p35 depending on the differentiation states of PC12 cells. These results indicate that Cdk5-p35 regulates L-, P/Q-, or N-type VDCCs in a cellular context-dependent manner. Calcium (Ca(2+) ) influx through voltage-dependent Ca(2+) channels (VDCCs) triggers neurotransmitter release from pre-synaptic terminal of neurons. The channel activity of VDCCs is regulated by Cdk5-p35, a neuronal Ser/Thr kinase. However, there have been debates about the regulation of VDCCs by Cdk5. Using PC12 cells, we show that Cdk5-p35 regulates VDCCs in a type (L, P/Q, and N) and differentiation-dependent manner. NGF = nerve growth factor. © 2014 International Society for Neurochemistry.

  1. Cytosolic ATP Relieves Voltage-Dependent Inactivation of T-Type Calcium Channels and Facilitates Excitability of Neurons in the Rat Central Medial Thalamus

    Science.gov (United States)

    Stamenic, Tamara Timic

    2018-01-01

    Abstract The central medial nucleus (CeM) is a part of the intralaminar thalamus, which is involved in the control of arousal and sensory processing. However, ionic conductances and mechanisms that regulate the activity of the CeM are not well studied. Here, we used in vitro electrophysiology in acute brain slices from adolescent rats to demonstrate that T-type calcium currents (T-currents) are prominent in the majority of the studied CeM neurons and are critical determinants of low-threshold calcium spikes (LTSs), which in turn regulate excitability of these neurons. Using an ATP-free internal solution decreased T-current density and induced a profound hyperpolarizing shift in steady-state inactivation curves while voltage-dependent activation kinetics were spared. Furthermore, selective pharmacological blockade of T-channels or use of an ATP-free solution reduced both tonic action potential (AP) frequency and rebound burst firing in CeM neurons. Our results indicate that T-channels are critical regulators of a thalamocortical circuit output and suggest that cytosolic ATP could be an endogenous regulatory mechanism in which T-channels may functionally gate sensory transmission and arousal in vivo. PMID:29468189

  2. Differential neuroprotective and anti-inflammatory effects of L-type voltage dependent calcium channel and ryanodine receptor antagonists in the substantia nigra and locus coeruleus.

    Science.gov (United States)

    Hopp, Sarah C; Royer, Sarah E; D'Angelo, Heather M; Kaercher, Roxanne M; Fisher, David A; Wenk, Gary L

    2015-03-01

    Neuroinflammation and degeneration of catecholaminergic brainstem nuclei occur early in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Neuroinflammation increases levels of pro-inflammatory cytokines and reactive oxygen species which can alter neuronal calcium (Ca(+2)) homoeostasis via L-type voltage dependent calcium channels (L-VDCCs) and ryanodine receptors (RyRs). Alterations in Ca(+2) channel activity in the SN and LC can lead to disruption of normal pacemaking activity in these areas, contributing to behavioral deficits. Here, we utilized an in vivo model of chronic neuroinflammation: rats were infused intraventricularly with a continuous small dose (0.25 μg/h) of lipopolysaccharide (LPS) or artificial cerebrospinal fluid (aCSF) for 28 days. Rats were treated with either the L-VDCC antagonist nimodipine or the RyR antagonist dantrolene. LPS-infused rats had significant motor deficits in the accelerating rotarod task as well as abnormal behavioral agitation in the forced swim task and open field. Corresponding with these behavioral deficits, LPS-infused rats also had significant increases in microglia activation and loss of tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra pars compacta (SNpc) and locus coeruleus (LC). Treatment with nimodipine or dantrolene normalized LPS-induced abnormalities in the rotarod and forced swim, restored the number of TH-immunoreactive cells in the LC, and significantly reduced microglia activation in the SNpc. Only nimodipine significantly reduced microglia activation in the LC, and neither drug increased TH immunoreactivity in the SNpc. These findings demonstrate that the Ca(+2) dysregulation in the LC and SN brainstem nuclei is differentially altered by chronic neuroinflammation. Overall, targeting Ca + 2 dysregulation may be an important target for ameliorating neurodegeneration in the SNpc and LC.

  3. Oxaliplatin administration increases expression of the voltage-dependent calcium channel α2δ-1 subunit in the rat spinal cord

    Directory of Open Access Journals (Sweden)

    Ken Yamamoto

    2016-02-01

    Full Text Available Oxaliplatin is a chemotherapeutic agent that is effective against various types of cancer including colorectal cancer. Acute cold hyperalgesia is a serious side effect of oxaliplatin treatment. Although the therapeutic drug pregabalin is beneficial for preventing peripheral neuropathic pain by targeting the voltage-dependent calcium channel α2δ-1 (Cavα2δ-1 subunit, the effect of oxaliplatin-induced acute cold hypersensitivity is uncertain. To analyze the contribution of the Cavα2δ-1 subunit to the development of oxaliplatin-induced acute cold hypersensitivity, Cavα2δ-1 subunit expression in the rat spinal cord was analyzed after oxaliplatin treatment. Behavioral assessment using the acetone spray test showed that 6 mg/kg oxaliplatin-induced cold hypersensitivity 2 and 4 days later. Oxaliplatin-induced acute cold hypersensitivity 4 days after treatment was significantly inhibited by pregabalin (50 mg/kg, p.o.. Oxaliplatin (6 mg/kg, i.p. treatment increased the expression level of Cavα2δ-1 subunit mRNA and protein in the spinal cord 2 and 4 days after treatment. Immunohistochemistry showed that oxaliplatin increased Cavα2δ-1 subunit protein expression in superficial layers of the spinal dorsal horn 2 and 4 days after treatment. These results suggest that oxaliplatin treatment increases Cavα2δ-1 subunit expression in the superficial layers of the spinal cord and may contribute to functional peripheral acute cold hypersensitivity.

  4. Voltage Dependence of a Neuromodulator-Activated Ionic Current123

    Science.gov (United States)

    2016-01-01

    Abstract The neuromodulatory inward current (IMI) generated by crab Cancer borealis stomatogastric ganglion neurons is an inward current whose voltage dependence has been shown to be crucial in the activation of oscillatory activity of the pyloric network of this system. It has been previously shown that IMI loses its voltage dependence in conditions of low extracellular calcium, but that this effect appears to be regulated by intracellular calmodulin. Voltage dependence is only rarely regulated by intracellular signaling mechanisms. Here we address the hypothesis that the voltage dependence of IMI is mediated by intracellular signaling pathways activated by extracellular calcium. We demonstrate that calmodulin inhibitors and a ryanodine antagonist can reduce IMI voltage dependence in normal Ca2+, but that, in conditions of low Ca2+, calmodulin activators do not restore IMI voltage dependence. Further, we show evidence that CaMKII alters IMI voltage dependence. These results suggest that calmodulin is necessary but not sufficient for IMI voltage dependence. We therefore hypothesize that the Ca2+/calmodulin requirement for IMI voltage dependence is due to an active sensing of extracellular calcium by a GPCR family calcium-sensing receptor (CaSR) and that the reduction in IMI voltage dependence by a calmodulin inhibitor is due to CaSR endocytosis. Supporting this, preincubation with an endocytosis inhibitor prevented W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride)-induced loss of IMI voltage dependence, and a CaSR antagonist reduced IMI voltage dependence. Additionally, myosin light chain kinase, which is known to act downstream of the CaSR, seems to play a role in regulating IMI voltage dependence. Finally, a Gβγ-subunit inhibitor also affects IMI voltage dependence, in support of the hypothesis that this process is regulated by a G-protein-coupled CaSR. PMID:27257619

  5. Coexpression of voltage-dependent calcium channels Cav1.2, 2.1a, and 2.1b in vascular myocytes

    DEFF Research Database (Denmark)

    Andreasen, Ditte; Friis, Ulla Glenert; Uhrenholt, Torben Rene

    2006-01-01

    Voltage-dependent Ca2+ channels Cav1.2 (L type) and Cav2.1 (P/Q type) are expressed in vascular smooth muscle cells (VSMCs) and are important for the contraction of renal resistance vessels. In the present study we examined whether native renal VSMCs coexpress L-, P-, and Q-type Ca2+ currents. Th...

  6. Coexpression of voltage-dependent calcium channels Cav1.2, 2.1a, and 2.1b in vascular myocytes

    DEFF Research Database (Denmark)

    Andreasen, Ditte; Friis, Ulla G; Uhrenholt, Torben R

    2006-01-01

    , and blocking P-type currents (omega-agatoxin IVA 10 nmol/L) led to 20.2+/-3.0% inhibition, whereas 300 nmol/L of omega agatoxin IVA (blocking P/Q-type) inhibited 45.0+/-7.3%. In rat aortic smooth muscle cells (A7r5), blockade of L-type channels resulted in 28.5+/-6.1% inhibition, simultaneous blockade of L....... The expression of both Cav2.1a (P-type) and Cav2.1b (Q-type) mRNA was demonstrated by RT-PCR in renal preglomerular vessels from rats and mice. Immunolabeling was performed on A7r5 cells, renal cryosections, and freshly isolated renal VSMCs with anti-Cav1.2 and anti-Cav2.1 antibodies. Conventional and confocal......-type and P-type channels inhibited 58.0+/-11.8%, and simultaneous inhibition of L-, P-, and Q-type channels led to blockade (88.7+/-5.6%) of the Ca2+ current. We conclude that aortic and renal preglomerular smooth muscle cells express L-, P-, and Q-type voltage-dependent Ca2+ channels in the rat and mouse....

  7. Genotypic to expression profiling of bovine calcium channel, voltage-dependent, alpha-2/delta subunit 1 gene, and their association with bovine mastitis among Frieswal (HFX Sahiwal) crossbred cattle of Indian origin.

    Science.gov (United States)

    Deb, Rajib; Singh, Umesh; Kumar, Sushil; Kumar, Arun; Singh, Rani; Sengar, Gyanendra; Mann, Sandeep; Sharma, Arjava

    2014-04-03

    Calcium channel, voltage-dependent, alpha-2/delta subunit 1 (CACNA2D1) gene is considered to be an important noncytokine candidate gene influencing mastitis. Scanty of reports are available until today regarding the role play of CACNA2D1 gene on the susceptibility of bovine mastitis. We interrogated the CACNA2D1 G519663A [A>G] SNP by PCR-RFLP among two hundreds Frieswal (HF X Sahiwal) crossbred cattle of Indian origin. Genotypic frequency of AA (51.5, n=101) was comparatively higher than AG (35, n=70) and GG (14.5, n=29). Association of Somatic cell score (SCS) with genotypes revealed that, GG genotypes showing lesser count (less susceptible to mastitis) compare to AA and AG. Relative expression of CACNA2D1 transcript (in milk samples) was significantly higher among GG than AG and AA. Further we have also isolated blood sample from the all groups and PBMCs were cultured from each blood sample as per the standard protocol. They were treated with Calcium channel blocker and the expression level of the CACNA2D1 gene was evaluated by Real Time PCR. Results show that expression level decline in each genotypic group after treatment and expression level of GG are again significantly higher than AA and AG. Thus, it may be concluded that GG genotypic animals are favorable for selecting disease resistant breeds.

  8. Identification of the Arg1086His mutation in the alpha subunit of the voltage-dependent calcium channel (CACNA1S) in a North American family with malignant hyperthermia.

    Science.gov (United States)

    Stewart, S L; Hogan, K; Rosenberg, H; Fletcher, J E

    2001-03-01

    Individuals from a large North American population were screened for the presence of the mutation in the alpha1 subunit of the voltage-dependent calcium channel (CACNA1S) that has recently been associated with malignant hyperthermia (MH). This Arg1086His mutation was screened for in 154 MH normal (MHN) individuals and 112 MH susceptible (MHS) individuals, who were diagnosed by the North American protocol of the in vitro contracture test. PCR and restriction enzyme analysis was used to test for the mutation. The Arg1086His mutation in the CACNA1S was not found in any of the MHN individuals. In contrast, two related individuals (grandfather and grandson, father and son of the MH proband) among the MHS group exhibited this mutation. However, a third MHS individual in the same family (granddaughter, cousin of the grandson) did not exhibit this mutation. These results indicate that this mutation may be associated with MH in this family. Genetic alterations in the CACNA1S associated with MH are present in approximately 1% of this North American MHS population.

  9. Voltage Dependence of Supercapacitor Capacitance

    Directory of Open Access Journals (Sweden)

    Szewczyk Arkadiusz

    2016-09-01

    Full Text Available Electronic Double-Layer Capacitors (EDLC, called Supercapacitors (SC, are electronic devices that are capable to store a relatively high amount of energy in a small volume comparing to other types of capacitors. They are composed of an activated carbon layer and electrolyte solution. The charge is stored on electrodes, forming the Helmholtz layer, and in electrolyte. The capacitance of supercapacitor is voltage- dependent. We propose an experimental method, based on monitoring of charging and discharging a supercapacitor, which enables to evaluate the charge in an SC structure as well as the Capacitance-Voltage (C-V dependence. The measurement setup, method and experimental results of charging/discharging commercially available supercapacitors in various voltage and current conditions are presented. The total charge stored in an SC structure is proportional to the square of voltage at SC electrodes while the charge on electrodes increases linearly with the voltage on SC electrodes. The Helmholtz capacitance increases linearly with the voltage bias while a sublinear increase of total capacitance was found. The voltage on SC increases after the discharge of electrodes due to diffusion of charges from the electrolyte to the electrodes. We have found that the recovery voltage value is linearly proportional to the initial bias voltage value.

  10. Calcium triggers reversal of calmodulin on nested anti-parallel sites in the IQ motif of the neuronal voltage-dependent sodium channel NaV1.2.

    Science.gov (United States)

    Hovey, Liam; Fowler, C Andrew; Mahling, Ryan; Lin, Zesen; Miller, Mark Stephen; Marx, Dagan C; Yoder, Jesse B; Kim, Elaine H; Tefft, Kristin M; Waite, Brett C; Feldkamp, Michael D; Yu, Liping; Shea, Madeline A

    2017-05-01

    Several members of the voltage-gated sodium channel family are regulated by calmodulin (CaM) and ionic calcium. The neuronal voltage-gated sodium channel Na V 1.2 contains binding sites for both apo (calcium-depleted) and calcium-saturated CaM. We have determined equilibrium dissociation constants for rat Na V 1.2 IQ motif [IQRAYRRYLLK] binding to apo CaM (~3nM) and (Ca 2+ ) 4 -CaM (~85nM), showing that apo CaM binding is favored by 30-fold. For both apo and (Ca 2+ ) 4 -CaM, NMR demonstrated that Na V 1.2 IQ motif peptide (Na V 1.2 IQp ) exclusively made contacts with C-domain residues of CaM (CaM C ). To understand how calcium triggers conformational change at the CaM-IQ interface, we determined a solution structure (2M5E.pdb) of (Ca 2+ ) 2 -CaM C bound to Na V 1.2 IQp . The polarity of (Ca 2+ ) 2 -CaM C relative to the IQ motif was opposite to that seen in apo CaM C -Na v 1.2 IQp (2KXW), revealing that CaM C recognizes nested, anti-parallel sites in Na v 1.2 IQp . Reversal of CaM may require transient release from the IQ motif during calcium binding, and facilitate a re-orientation of CaM N allowing interactions with non-IQ Na V 1.2 residues or auxiliary regulatory proteins interacting in the vicinity of the IQ motif. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Human neuronal stargazin-like proteins, γ2, γ3 and γ4; an investigation of their specific localization in human brain and their influence on CaV2.1 voltage-dependent calcium channels expressed in Xenopus oocytes.

    Directory of Open Access Journals (Sweden)

    Dolphin Annette C

    2003-09-01

    Full Text Available Abstract Background Stargazin (γ2 and the closely related γ3, and γ4 transmembrane proteins are part of a family of proteins that may act as both neuronal voltage-dependent calcium channel (VDCC γ subunits and transmembrane α-amino-3-hydroxy-5-methyl-4-isoxazoleproponinc (AMPA receptor regulatory proteins (TARPs. In this investigation, we examined the distribution patterns of the stargazin-like proteins γ2, γ3, and γ4 in the human central nervous system (CNS. In addition, we investigated whether human γ2 or γ4 could modulate the electrophysiological properties of a neuronal VDCC complex transiently expressed in Xenopus oocytes. Results The mRNA encoding human γ2 is highly expressed in cerebellum, cerebral cortex, hippocampus and thalamus, whereas γ3 is abundant in cerebral cortex and amygdala and γ4 in the basal ganglia. Immunohistochemical analysis of the cerebellum determined that both γ2 and γ4 are present in the molecular layer, particularly in Purkinje cell bodies and dendrites, but have an inverse expression pattern to one another in the dentate cerebellar nucleus. They are also detected in the interneurons of the granule cell layer though only γ2 is clearly detected in granule cells. The hippocampus stains for γ2 and γ4 throughout the layers of the every CA region and the dentate gyrus, whilst γ3 appears to be localized particularly to the pyramidal and granule cell bodies. When co-expressed in Xenopus oocytes with a CaV2.1/β4 VDCC complex, either in the absence or presence of an α2δ2 subunit, neither γ2 nor γ4 significantly modulated the VDCC peak current amplitude, voltage-dependence of activation or voltage-dependence of steady-state inactivation. Conclusion The human γ2, γ3 and γ4 stargazin-like proteins are detected only in the CNS and display differential distributions among brain regions and several cell types in found in the cerebellum and hippocampus. These distribution patterns closely resemble those

  12. Noncompetitive, Voltage-Dependent NMDA Receptor Antagonism by Hydrophobic Anions

    Science.gov (United States)

    Linsenbardt, Andrew J.; Chisari, Mariangela; Yu, Andrew; Shu, Hong-Jin; Zorumski, Charles F.

    2013-01-01

    NMDA receptor (NMDAR) antagonists are dissociative anesthetics, drugs of abuse, and are of therapeutic interest in neurodegeneration and neuropsychiatric disease. Many well-known NMDAR antagonists are positively charged, voltage-dependent channel blockers. We recently showed that the hydrophobic anion dipicrylamine (DPA) negatively regulates GABAA receptor function by a mechanism indistinguishable from that of sulfated neurosteroids. Because sulfated neurosteroids also modulate NMDARs, here we examined the effects of DPA on NMDAR function. In rat hippocampal neurons DPA inhibited currents gated by 300 µM NMDA with an IC50 of 2.3 µM. Neither onset nor offset of antagonism exhibited dependence on channel activation but exhibited a noncompetitive profile. DPA antagonism was independent of NMDAR subunit composition and was similar at extrasynaptic and total receptor populations. Surprisingly, similar to cationic channel blockers but unlike sulfated neurosteroids, DPA antagonism was voltage dependent. Onset and offset of DPA antagonism were nearly 10-fold faster than DPA-induced increases in membrane capacitance, suggesting that membrane interactions do not directly explain antagonism. Furthermore, voltage dependence did not derive from association of DPA with a site on NMDARs directly accessible to the outer membrane leaflet, assessed by DPA translocation experiments. Consistent with the expected lack of channel block, DPA antagonism did not interact with permeant ions. Therefore, we speculate that voltage dependence may arise from interactions of DPA with the inherent voltage dependence of channel gating. Overall, we conclude that DPA noncompetitively inhibits NMDA-induced current by a novel voltage-dependent mechanism and represents a new class of anionic NMDAR antagonists. PMID:23144238

  13. Manipulating the voltage dependence of tunneling spin torques

    KAUST Repository

    Manchon, Aurelien

    2012-10-01

    Voltage-driven spin transfer torques in magnetic tunnel junctions provide an outstanding tool to design advanced spin-based devices for memory and reprogrammable logic applications. The non-linear voltage dependence of the torque has a direct impact on current-driven magnetization dynamics and on devices performances. After a brief overview of the progress made to date in the theoretical description of the spin torque in tunnel junctions, I present different ways to alter and control the bias dependence of both components of the spin torque. Engineering the junction (barrier and electrodes) structural asymmetries or controlling the spin accumulation profile in the free layer offer promising tools to design effcient spin devices.

  14. Voltage-dependent block of charge movement components by nifedipine in frog skeletal muscle.

    Science.gov (United States)

    Huang, C L

    1990-09-01

    Potential-dependent inhibition of charge movement components by nifedipine was studied in intact, voltage-clamped, frog skeletal muscle fibers. Available charge was reduced by small shifts in holding potential (from -100 mV to -70 mV) in 2 microM nifedipine, without changes in the capacitance deduced from control (-120 mV to -100 mV) voltage steps made at a fully polarized (-100 mV) holding potential. These voltage-dependent effects did not occur in lower (0-0.5 microM) nifedipine concentrations. The voltage dependence of membrane capacitance at higher (10 microM) nifedipine concentrations was reduced even in fully polarized fibers, but shifting the holding voltage produced no further block. Voltage-dependent inhibition by nifedipine was associated with a fall in available charge, and a reduction in the charge and capacitance-voltage relationships and of late (q gamma) charging transients. It thus separated a membrane-capacitance with a distinct and steep steady-state voltage dependence. Tetracaine (2 mM) reduced voltage-dependent membrane capacitance and nonlinear charge more than did nifedipine. However, nifedipine did not exert voltage-dependent effects on charging currents, membrane capacitance, or inactivation of tetracaine-resistant (q beta) charge. This excludes participation of q beta, or the membrane charge as a whole, from the voltage-dependent effects of nifedipine. Rather, the findings suggest that the charge susceptible to potential-dependent block by nifedipine falls within the tetracaine-sensitive (q gamma) category of intramembrane charge.

  15. Voltage-dependent K+channels improve the energy efficiency of signalling in blowfly photoreceptors.

    Science.gov (United States)

    Heras, Francisco J H; Anderson, John; Laughlin, Simon B; Niven, Jeremy E

    2017-04-01

    Voltage-dependent conductances in many spiking neurons are tuned to reduce action potential energy consumption, so improving the energy efficiency of spike coding. However, the contribution of voltage-dependent conductances to the energy efficiency of analogue coding, by graded potentials in dendrites and non-spiking neurons, remains unclear. We investigate the contribution of voltage-dependent conductances to the energy efficiency of analogue coding by modelling blowfly R1-6 photoreceptor membrane. Two voltage-dependent delayed rectifier K + conductances (DRs) shape the membrane's voltage response and contribute to light adaptation. They make two types of energy saving. By reducing membrane resistance upon depolarization they convert the cheap, low bandwidth membrane needed in dim light to the expensive high bandwidth membrane needed in bright light. This investment of energy in bandwidth according to functional requirements can halve daily energy consumption. Second, DRs produce negative feedback that reduces membrane impedance and increases bandwidth. This negative feedback allows an active membrane with DRs to consume at least 30% less energy than a passive membrane with the same capacitance and bandwidth. Voltage-dependent conductances in other non-spiking neurons, and in dendrites, might be organized to make similar savings. © 2017 The Author(s).

  16. Vector spin modeling for magnetic tunnel junctions with voltage dependent effects

    International Nuclear Information System (INIS)

    Manipatruni, Sasikanth; Nikonov, Dmitri E.; Young, Ian A.

    2014-01-01

    Integration and co-design of CMOS and spin transfer devices requires accurate vector spin conduction modeling of magnetic tunnel junction (MTJ) devices. A physically realistic model of the MTJ should comprehend the spin torque dynamics of nanomagnet interacting with an injected vector spin current and the voltage dependent spin torque. Vector spin modeling allows for calculation of 3 component spin currents and potentials along with the charge currents/potentials in non-collinear magnetic systems. Here, we show 4-component vector spin conduction modeling of magnetic tunnel junction devices coupled with spin transfer torque in the nanomagnet. Nanomagnet dynamics, voltage dependent spin transport, and thermal noise are comprehended in a self-consistent fashion. We show comparison of the model with experimental magnetoresistance (MR) of MTJs and voltage degradation of MR with voltage. Proposed model enables MTJ circuit design that comprehends voltage dependent spin torque effects, switching error rates, spin degradation, and back hopping effects

  17. The voltage-dependent action of pentobarbital on batrachotoxin-modified human brain sodium channels.

    Science.gov (United States)

    Rehberg, B; Duch, D S; Urban, B W

    1994-09-14

    The voltage-dependent action of the intravenous anesthetic pentobarbital on human brain sodium channels activated by batrachotoxin was examined using planar lipid bilayer methods. Fractional open time-data were fitted by Boltzmann functions to yield simple parameters characterizing the voltage-dependence of the fractional open time. Pentobarbital caused a dose-dependent reduction of the maximum fractional open time of the sodium channel and a shift of the potential of half-maximal open time towards hyperpolarized potentials, whereas the slope parameter of the Boltzmann-fits was unaffected. A statistically significant increase of the variability of these parameters was found only in the case of the maximum fractional open time, indicating a random fluctuation of pentobarbital-induced suppression of the sodium channels over time. The voltage-dependent action of pentobarbital probably results from either a pentobarbital-modification of channel activation gating and/or a modification of the pentobarbital action by the gating process itself.

  18. Calcium

    Science.gov (United States)

    ... absorb calcium as well. Sufficient calcium intake from food, and supplements if needed, can slow the rate of bone loss. Women of childbearing ... calcium absorption. People who eat a variety of foods don't have to consider ... include consumption of alcohol- and caffeine-containing beverages as well ...

  19. Voltage-dependent activation in purified reconstituted sodium channels from rabbit T-tubular membranes

    Energy Technology Data Exchange (ETDEWEB)

    Furman, R.E.; Tanaka, J.C.; Mueller, P.; Barchi, R.L.

    1986-01-01

    The authors have examined the voltage-dependent gating of batrachotoxin-modified sodium channels purified from rabbit T-tubular membranes in two ways. First, purified channels were reconstituted into planar bilayers and single-channel properties were measured. Batrachotoxin-activated channels showed steep voltage-dependent activation with half-maximal opening probabilities at potentials between -95 and -116 mV. The single-channel conductance averaged 20 pS and was independent of membrane potential. A second approach was used to establish that this voltage dependence was a characteristic of the entire population of purified channels and not just those few channels observed in planar bilayers. Channels reconstituted into egg phosphophatidyl-choline vesicles were functionally oriented by inclusion of internal saxitoxin; vesicle membrane potentials were then generated by K/sup +/ gradients in the presence of valinomycin. All of the specific /sup 22/Na/sup +/ influx activated by batrachotoxin and blocked by saxitoxin was found to be voltage sensitive, activating between predicted membrane potentials of -100 and -50 mV. The single-channel properties of the purified T-tubular sodium channel correspond closely to those seen with native sodium channels from rat sarcolemma. The voltage-dependent activation of the bactrachotoxin-modified reconstituted channel is the same as that seen with native channels in situ or in bilayers after exposure this toxin.

  20. Calcium

    Science.gov (United States)

    ... and blood vessels contract and expand, to secrete hormones and enzymes and to send messages through the nervous system. It is important to get plenty of calcium in the foods you eat. Foods rich in calcium include Dairy products such as milk, cheese, and yogurt Leafy, green vegetables Fish with ...

  1. Cation gating and selectivity in a purified, reconstituted, voltage-dependent sodium channel

    International Nuclear Information System (INIS)

    Barchi, R.L.; Tanaka, J.C.

    1984-01-01

    In excitable membranes, the voltage-dependent sodium channel controls the primary membrane conductance change necessary for the generation of an action potential. Over the past four decades, the time- and voltage-dependent sodium currents gated by this channel have been thoroughly documented with increasingly sophisticated voltage-clamp techniques. Recent advances in the biochemistry of membrane proteins have led to the solubilization and purification of this channel protein from nerve (6) and from muscle (4) or muscle-derived (1) membranes, and have provided an approach to the correlation of the channel's molecular structure with its functional properties. Each of these sodium channel preparations appears to contain a large glycoprotein either as its sole component (2) or in association with several small subunits (6, 3). Evidence that these purified proteins represent the excitable membrane sodium channel is presented. 8 refs., 1 fig., 1 tab

  2. Ca2+ and voltage dependence of cardiac ryanodine receptor channel block by sphingosylphosphorylcholine.

    Science.gov (United States)

    Yasukochi, Midori; Uehara, Akira; Kobayashi, Sei; Berlin, Joshua R

    2003-03-01

    The effect of sphingosylphosphorylcholine (SPC) on the cytoplasmic Ca(2+) and voltage dependence of channel gating by cardiac ryanodine receptors (RyR) was examined in lipid bilayer experiments. Micromolar concentrations of the lysosphingolipid SPC added to cis solutions rapidly and reversibly decreased the single-channel open probability (P(o)) of reconstituted RyR channels. The SPC-induced decrease in P(o) was marked by an increase in mean closed time and burst-like channel gating. Gating kinetics during intraburst periods were unchanged from those observed in the absence of the sphingolipid, although SPC induced a long-lived closed state that appeared to explain the observed decrease in channel P(o). SPC effects were observed over a broad range of cis [Ca(2+)] but were not competitive with Ca(2+). Interestingly, the sphingolipid-induced, long-lived closed state displayed voltage-dependent kinetics, even though other channel gating kinetics were not sensitive to voltage. Assuming SPC effects represent channel blockade, these results suggest that the blocking rate is independent of voltage whereas the unblocking rate is voltage dependent. Together, these results suggest that SPC binds directly to the cytoplasmic side of the RyR protein in a location in or near the membrane dielectric, but distinct from cytoplasmic Ca(2+) binding sites on the protein.

  3. KCNE5 Induces Time- and Voltage-Dependent Modulation of the KCNQ1 Current

    OpenAIRE

    Angelo, Kamilla; Jespersen, Thomas; Grunnet, Morten; Nielsen, Morten Schak; Klaerke, Dan A.; Olesen, Søren-Peter

    2002-01-01

    The function of the KCNE5 (KCNE1-like) protein has not previously been described. Here we show that KCNE5 induces both a time- and voltage-dependent modulation of the KCNQ1 current. Interaction of the KCNQ1 channel with KCNE5 shifted the voltage activation curve of KCNQ1 by more than 140 mV in the positive direction. The activation threshold of the KCNQ1+KCNE5 complex was +40 mV and the midpoint of activation was +116 mV. The KCNQ1+KCNE5 current activated slowly and deactivated rapidly as com...

  4. Voltage-dependent block of charge movement components by nifedipine in frog skeletal muscle

    OpenAIRE

    1990-01-01

    Potential-dependent inhibition of charge movement components by nifedipine was studied in intact, voltage-clamped, frog skeletal muscle fibers. Available charge was reduced by small shifts in holding potential (from -100 mV to -70 mV) in 2 microM nifedipine, without changes in the capacitance deduced from control (-120 mV to -100 mV) voltage steps made at a fully polarized (-100 mV) holding potential. These voltage-dependent effects did not occur in lower (0-0.5 microM) nifedipine concentrati...

  5. Cellular elements for seeing in the dark: voltage-dependent conductances in cockroach photoreceptors

    Directory of Open Access Journals (Sweden)

    Salmela Iikka

    2012-08-01

    Full Text Available Abstract Background The importance of voltage-dependent conductances in sensory information processing is well-established in insect photoreceptors. Here we present the characterization of electrical properties in photoreceptors of the cockroach (Periplaneta americana, a nocturnal insect with a visual system adapted for dim light. Results Whole-cell patch-clamped photoreceptors had high capacitances and input resistances, indicating large photosensitive rhabdomeres suitable for efficient photon capture and amplification of small photocurrents at low light levels. Two voltage-dependent potassium conductances were found in the photoreceptors: a delayed rectifier type (KDR and a fast transient inactivating type (KA. Activation of KDR occurred during physiological voltage responses induced by light stimulation, whereas KA was nearly fully inactivated already at the dark resting potential. In addition, hyperpolarization of photoreceptors activated a small-amplitude inward-rectifying (IR current mediated at least partially by chloride. Computer simulations showed that KDR shapes light responses by opposing the light-induced depolarization and speeding up the membrane time constant, whereas KA and IR have a negligible role in the majority of cells. However, larger KA conductances were found in smaller and rapidly adapting photoreceptors, where KA could have a functional role. Conclusions The relative expression of KA and KDR in cockroach photoreceptors was opposite to the previously hypothesized framework for dark-active insects, necessitating further comparative work on the conductances. In general, the varying deployment of stereotypical K+ conductances in insect photoreceptors highlights their functional flexibility in neural coding.

  6. Inhibition of large conductance calcium-dependent potassium ...

    African Journals Online (AJOL)

    conductance, calcium and voltage- dependent potassium (BKCa) channels thereby promoting vasoconstriction. Our results show that the Rho-kinase inhibitor, Y-27632, induced concentration-dependent relaxation in rat mesenteric artery.

  7. The Eag domain regulates the voltage-dependent inactivation of rat Eag1 K+ channels.

    Directory of Open Access Journals (Sweden)

    Ting-Feng Lin

    Full Text Available Eag (Kv10 and Erg (Kv11 belong to two distinct subfamilies of the ether-à-go-go K+ channel family (KCNH. While Erg channels are characterized by an inward-rectifying current-voltage relationship that results from a C-type inactivation, mammalian Eag channels display little or no voltage-dependent inactivation. Although the amino (N-terminal region such as the eag domain is not required for the C-type inactivation of Erg channels, an N-terminal deletion in mouse Eag1 has been shown to produce a voltage-dependent inactivation. To further discern the role of the eag domain in the inactivation of Eag1 channels, we generated N-terminal chimeras between rat Eag (rEag1 and human Erg (hERG1 channels that involved swapping the eag domain alone or the complete cytoplasmic N-terminal region. Functional analyses indicated that introduction of the homologous hERG1 eag domain led to both a fast phase and a slow phase of channel inactivation in the rEag1 chimeras. By contrast, the inactivation features were retained in the reverse hERG1 chimeras. Furthermore, an eag domain-lacking rEag1 deletion mutant also showed the fast phase of inactivation that was notably attenuated upon co-expression with the rEag1 eag domain fragment, but not with the hERG1 eag domain fragment. Additionally, we have identified a point mutation in the S4-S5 linker region of rEag1 that resulted in a similar inactivation phenotype. Biophysical analyses of these mutant constructs suggested that the inactivation gating of rEag1 was distinctly different from that of hERG1. Overall, our findings are consistent with the notion that the eag domain plays a critical role in regulating the inactivation gating of rEag1. We propose that the eag domain may destabilize or mask an inherent voltage-dependent inactivation of rEag1 K+ channels.

  8. Skin secretion of Siphonops paulensis (Gymnophiona, Amphibia forms voltage-dependent ionic channels in lipid membranes

    Directory of Open Access Journals (Sweden)

    E.F. Schwartz

    2003-09-01

    Full Text Available The effect of the skin secretion of the amphibian Siphonops paulensis was investigated by monitoring the changes in conductance of an artificial planar lipid bilayer. Skin secretion was obtained by exposure of the animals to ether-saturated air, and then rinsing the animals with distilled water. Artificial lipid bilayers were obtained by spreading a solution of azolectin over an aperture of a Delrin cup inserted into a cut-away polyvinyl chloride block. In 9 of 12 experiments, the addition of the skin secretion to lipid bilayers displayed voltage-dependent channels with average unitary conductance of 258 ± 41.67 pS, rather than nonspecific changes in bilayer conductance. These channels were not sensitive to 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid or tetraethylammonium ion, but the experimental protocol used does not permit us to specify their characteristics.

  9. A non-linear voltage dependent charge movement in frog skeletal muscle.

    Science.gov (United States)

    Chandler, W K; Rakowski, R F; Schneider, M F

    1976-01-01

    1. Voltage-clamp experiments were carried out using the three microelectrode technique. Using this method membrane current density at V1 is proportional to deltaV( = V2 - V1) where V1 and V2 are voltages at distances 1 and 21 from the end of a fibre. Voltage dependent sodium currents were blocked by tetrodotoxin, potassium by tetraethylammonium ions and rubidium. Contraction was blocked by adding sucrose, 467 mM. 2. The current deltaV (control) associated with a positive voltage step from a hyperpolarized conditioning voltage to the holding potential, -80 mV, showed two components, a capacitative transient which decayed rapidly and a maintained steady level...

  10. Tracking voltage-dependent conformational changes in skeletal muscle sodium channel during activation.

    Science.gov (United States)

    Chanda, Baron; Bezanilla, Francisco

    2002-11-01

    The primary voltage sensor of the sodium channel is comprised of four positively charged S4 segments that mainly differ in the number of charged residues and are expected to contribute differentially to the gating process. To understand their kinetic and steady-state behavior, the fluorescence signals from the sites proximal to each of the four S4 segments of a rat skeletal muscle sodium channel were monitored simultaneously with either gating or ionic currents. At least one of the kinetic components of fluorescence from every S4 segment correlates with movement of gating charge. The fast kinetic component of fluorescence from sites S216C (S4 domain I), S660C (S4 domain II), and L1115C (S4 domain III) is comparable to the fast component of gating currents. In contrast, the fast component of fluorescence from the site S1436C (S4 domain IV) correlates with the slow component of gating. In all the cases, the slow component of fluorescence does not have any apparent correlation with charge movement. The fluorescence signals from sites reflecting the movement of S4s in the first three domains initiate simultaneously, whereas the fluorescence signals from the site S1436C exhibit a lag phase. These results suggest that the voltage-dependent movement of S4 domain IV is a later step in the activation sequence. Analysis of equilibrium and kinetic properties of fluorescence over activation voltage range indicate that S4 domain III is likely to move at most hyperpolarized potentials, whereas the S4s in domain I and domain II move at more depolarized potentials. The kinetics of fluorescence changes from sites near S4-DIV are slower than the activation time constants, suggesting that the voltage-dependent movement of S4-DIV may not be a prerequisite for channel opening. These experiments allow us to map structural features onto the kinetic landscape of a sodium channel during activation.

  11. PIP2 regulation of KCNQ channels: biophysical and molecular mechanisms for lipid modulation of voltage-dependent gating

    Directory of Open Access Journals (Sweden)

    Mark Alan Zaydman

    2014-05-01

    Full Text Available Voltage-gated potassium (Kv channels contain voltage-sensing (VSD and pore-gate (PGD structural domains. During voltage-dependent gating, conformational changes in the two domains are coupled giving rise to voltage-dependent opening of the channel. In addition to membrane voltage, KCNQ (Kv7 channel opening requires the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2. Recent studies suggest that PIP2 serves as a cofactor to mediate VSD-PGD coupling in KCNQ1 channels. In this review, we put these findings in the context of the current understanding of voltage-dependent gating, lipid modulation of Kv channel activation, and PIP2-regulation of KCNQ channels. We suggest that lipid-mediated coupling of functional domains is a common mechanism among KCNQ channels that may be applicable to other Kv channels and membrane proteins.

  12. Over Expression of Voltage Dependent Anion Channel 2 (VDAC2 in Muscles of Electrically Stunned Chickens

    Directory of Open Access Journals (Sweden)

    Norshahida Abu Samah, Azura Amid, and Faridah Yusof

    2011-12-01

    Full Text Available Water bath stunning is a common practice in commercial slaughterhouses. Such treatment is economic and in line with animal welfare practice. However, the conditions applied for the stunning process may vary from a slaughterhouse to another slaughterhouse. Such a loose regulation on the stunning procedure has opened up doors for food adulteration such as over dose stunning. In this study, a simple and reliable approach using proteomics have been developed to study the effect of different currents and voltages in stunning on the protein expression of the chickens. Protein profiles of the chickens were constructed in order to detect any differences in protein expression and modifications. The different voltage studied were 10 V, 40 V and 70 V while the values for current studied were 0.25 A, 0.5 A, and 0.75 A. After the proteomics analyses using 2D Platinum ImageMaster 6.0 and Matrix-assisted laser desorption ionization- time of flight (MALDI TOF spectrometry identification, Voltage dependent anion channel 2 (VDAC2 was identified to be over expressed in the muscle sample of over stunned chicken. The over expression of VDAC2 was confirmed at the transcriptional level of RNA expression. Real Time PCR showed that all over stunned samples contained higher mRNA expression level for VDAC2 genes. The mRNA level of VDAC2 was up-regulated by 59.87 fold change when normalized with housekeeping gene. In conclusion, VDAC2 could serve as potential biomarkers for identification of electrically stimulated chickens. The existence of these biomarkers will help to monitor the slaughtering and stunning process in the future. It will revolutionize the food authentication field and give a new breathe to the meat industry.ABSTRAK: Kaedah "waterbath stunning" merupakan amalan biasa di pusat-pusat penyembelihan. Kaedah ini adalah ekonomik dan selari dengan amalan kebajikan haiwan. Walaubagaimanapun, syarat-syarat yang digunakan untuk proses kejutan tersebut mungkin

  13. The transmembrane domain and acidic lipid flip-flop regulates voltage-dependent fusion mediated by class II and III viral proteins.

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    Ruben M Markosyan

    Full Text Available Voltage dependence of fusion induced by class II and class III viral fusion proteins was investigated. Class II proteins from Ross River and Sindbus virus and a mutant class III protein from Epstein Barr virus were found to induce cell-cell fusion that is voltage dependent. Combined with previous studies, in all, four class II and two class III protein have now been shown to exhibit voltage-dependent fusion, demonstrating that this is probably a general phenomenon for these two classes of viral fusion proteins. In the present study, monitoring fusion of pseudovirus expressing Vesicular Stomatitis virus (VSV G within endosomes shows that here, too, fusion is voltage dependent. This supports the claim that voltage dependence of fusion is biologically relevant and that cell-cell fusion reliably models the voltage dependence. Fusion induced by class I viral proteins is independent of voltage; chimeras expressing the ectodomain of a class I fusion protein and the transmembrane domain of VSV G could therefore be used to explore the location within the protein responsible for voltage dependence. Results showed that the transmembrane domain is the region associated with voltage dependence. Experiments in which cells were enriched with acidic lipids led to the conclusion that it is the flip-flop of acidic lipids that carries the charge responsible for the observed voltage dependence of fusion. This flip-flop occurred downstream of hemifusion, in accord with previous findings that the voltage dependent steps of fusion occur at a stage subsequent to hemifusion.

  14. Ropivacaine-Induced Contraction Is Attenuated by Both Endothelial Nitric Oxide and Voltage-Dependent Potassium Channels in Isolated Rat Aortae

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    Seong-Ho Ok

    2013-01-01

    Full Text Available This study investigated endothelium-derived vasodilators and potassium channels involved in the modulation of ropivacaine-induced contraction. In endothelium-intact rat aortae, ropivacaine concentration-response curves were generated in the presence or absence of the following inhibitors: the nonspecific nitric oxide synthase (NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, the neuronal NOS inhibitor Nω-propyl-L-arginine hydrochloride, the inducible NOS inhibitor 1400W dihydrochloride, the nitric oxide-sensitive guanylyl cyclase (GC inhibitor ODQ, the NOS and GC inhibitor methylene blue, the phosphoinositide-3 kinase inhibitor wortmannin, the cytochrome p450 epoxygenase inhibitor fluconazole, the voltage-dependent potassium channel inhibitor 4-aminopyridine (4-AP, the calcium-activated potassium channel inhibitor tetraethylammonium (TEA, the inward-rectifying potassium channel inhibitor barium chloride, and the ATP-sensitive potassium channel inhibitor glibenclamide. The effect of ropivacaine on endothelial nitric oxide synthase (eNOS phosphorylation in human umbilical vein endothelial cells was examined by western blotting. Ropivacaine-induced contraction was weaker in endothelium-intact aortae than in endothelium-denuded aortae. L-NAME, ODQ, and methylene blue enhanced ropivacaine-induced contraction, whereas wortmannin, Nω-propyl-L-arginine hydrochloride, 1400W dihydrochloride, and fluconazole had no effect. 4-AP and TEA enhanced ropivacaine-induced contraction; however, barium chloride and glibenclamide had no effect. eNOS phosphorylation was induced by ropivacaine. These results suggest that ropivacaine-induced contraction is attenuated primarily by both endothelial nitric oxide and voltage-dependent potassium channels.

  15. Voltage Dependent Anion Channel Is Redistributed during Japanese Encephalitis Virus Infection of Insect Cells

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    Chanida Fongsaran

    2014-01-01

    Full Text Available Despite the availability of an effective vaccine, Japanese encephalitis remains a significant cause of morbidity and mortality in many parts of Asia. Japanese encephalitis is caused by the Japanese encephalitis virus (JEV, a mosquito transmitted flavivirus. Many of the details of the virus replication cycle in mosquito cells remain unknown. This study sought to determine whether GRP78, a well-characterized flavivirus E protein interacting protein, interacted with JEV E protein in insect cells, and whether this interaction was mediated at the cell surface. GRP78 was shown to interact with JEV E protein by coimmunoprecipitation, and was additionally shown to interact with voltage dependent anion protein (VDAC through the same methodology. Antibody inhibition experiments showed that neither GRP78 nor VDAC played a role in JEV internalization to insect cells. Interestingly, VDAC was shown to be significantly relocalized in response to JEV infection, and significant levels of colocalization between VDAC and GRP78 and VDAC and ribosomal L28 protein were seen in JEV infected but not uninfected cells. This is the first report of relocalization of VDAC in response to JEV infection and suggests that this may be a part of the JEV replication strategy in insect cells.

  16. Regulation of KV channel voltage-dependent activation by transmembrane β subunits

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    Xiaohui eSun

    2012-04-01

    Full Text Available Voltage-activated K+ (KV channels are important for shaping action potentials and maintaining resting membrane potential in excitable cells. KV channels contain a central pore-gate domain (PGD surrounded by four voltage-sensing domains (VSD. The VSDs will change conformation in response to alterations of the membrane potential thereby inducing the opening of the PGD. Many KV channels are heteromeric protein complexes containing auxiliary β subunits. These β subunits modulate channel expression and activity to increase functional diversity and render tissue specific phenotypes. This review focuses on the KV β subunits that contain transmembrane (TM segments including the KCNE family and the β subunits of large conductance, Ca2+- and voltage-activated K+ (BK channels. These TM β subunits affect the voltage-dependent activation of KV α subunits. Experimental and computational studies have described the structural location of these β subunits in the channel complexes and the biophysical effects on VSD activation, PGD opening and VSD-PGD coupling. These results reveal some common characteristics and mechanistic insights into KV channel modulation by TM β subunits.

  17. KCNE5 induces time- and voltage-dependent modulation of the KCNQ1 current

    DEFF Research Database (Denmark)

    Angelo, Kamilla; Jespersen, Thomas; Grunnet, Morten

    2002-01-01

    The function of the KCNE5 (KCNE1-like) protein has not previously been described. Here we show that KCNE5 induces both a time- and voltage-dependent modulation of the KCNQ1 current. Interaction of the KCNQ1 channel with KCNE5 shifted the voltage activation curve of KCNQ1 by more than 140 m......V in the positive direction. The activation threshold of the KCNQ1+KCNE5 complex was +40 mV and the midpoint of activation was +116 mV. The KCNQ1+KCNE5 current activated slowly and deactivated rapidly as compared to the KCNQ1+KCNE1 at 22 degrees C; however, at physiological temperature, the activation time constant...... of the KCNQ1+KCNE5 current decreased fivefold, thus exceeding the activation rate of the KCNQ1+KCNE1 current. The KCNE5 subunit is specific for the KCNQ1 channel, as none of other members of the KCNQ-family or the human ether a-go-go related channel (hERG1) was affected by KCNE5. Four residues...

  18. Molecular mechanism of allosteric modification of voltage-dependent sodium channels by local anesthetics.

    Science.gov (United States)

    Arcisio-Miranda, Manoel; Muroi, Yukiko; Chowdhury, Sandipan; Chanda, Baron

    2010-11-01

    The hallmark of many intracellular pore blockers such as tetra-alkylammonium compounds and local anesthetics is their ability to allosterically modify the movement of the voltage sensors in voltage-dependent ion channels. For instance, the voltage sensor of domain III is specifically stabilized in the activated state when sodium currents are blocked by local anesthetics. The molecular mechanism underlying this long-range interaction between the blocker-binding site in the pore and voltage sensors remains poorly understood. Here, using scanning mutagenesis in combination with voltage clamp fluorimetry, we systematically evaluate the role of the internal gating interface of domain III of the sodium channel. We find that several mutations in the S4-S5 linker and S5 and S6 helices dramatically reduce the stabilizing effect of lidocaine on the activation of domain III voltage sensor without significantly altering use-dependent block at saturating drug concentrations. In the wild-type skeletal muscle sodium channel, local anesthetic block is accompanied by a 21% reduction in the total gating charge. In contrast, point mutations in this critical intracellular region reduce this charge modification by local anesthetics. Our analysis of a simple model suggests that these mutations in the gating interface are likely to disrupt the various coupling interactions between the voltage sensor and the pore of the sodium channel. These findings provide a molecular framework for understanding the mechanisms underlying allosteric interactions between a drug-binding site and voltage sensors.

  19. Mitochondrial membrane cholesterol, the voltage dependent anion channel (VDAC), and the Warburg effect.

    Science.gov (United States)

    Campbell, Andrew M; Chan, Samuel H P

    2008-06-01

    Normal cells of aerobic organisms synthesize the energy they require in the form of ATP via the process of oxidative phosphorylation. This complex system resides in the mitochondria of cells and utilizes oxygen to produce a majority of cellular ATP. However, in most tumors, especially those with elevated cholesterogenesis, there is an increased reliance on glycolysis for energy, even in conditions where oxygen is available. This aerobic glycolysis (the Warburg effect) has far reaching ramifications on the tumor itself and the cells that surround it. In this brief review, we will discuss how abnormally high membrane cholesterol levels can result in a subsequent deficiency of oxidative energy production in mitochondria from cultured Morris hepatoma cells (MH-7777). We have identified the voltage dependent anion channel (VDAC) as a necessary component of a protein complex involved in mitochondrial membrane cholesterol distribution and transport. Work in our laboratory demonstrates that the ability of VDAC to influence mitochondrial membrane cholesterol distribution may have implications on mitochondrial characteristics such as oxidative phosphorylation and induction of apoptosis, as well as the propensity of cancer cells to exhibit a glycolytic phenotype.

  20. A CACNA1C variant associated with reduced voltage-dependent inactivation, increased CaV1.2 channel window current, and arrhythmogenesis.

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    Jessica A Hennessey

    Full Text Available Mutations in CACNA1C that increase current through the CaV1.2 L-type Ca2+ channel underlie rare forms of long QT syndrome (LQTS, and Timothy syndrome (TS. We identified a variant in CACNA1C in a male child of Filipino descent with arrhythmias and extracardiac features by candidate gene sequencing and performed functional expression studies to electrophysiologically characterize the effects of the variant on CaV1.2 channels. As a baby, the subject developed seizures and displayed developmental delays at 30 months of age. At age 5 years, he displayed a QTc of 520 ms and experienced recurrent VT. Physical exam at 17 years of age was notable for microcephaly, short stature, lower extremity weakness and atrophy with hyperreflexia, spastic diplegia, multiple dental caries and episodes of rhabdomyolysis. Candidate gene sequencing identified a G>C transversion at position 5731 of CACNA1C (rs374528680 predicting a glycine>arginine substitution at residue 1911 (p.G1911R of CaV1.2. The allele frequency of this variant is 0.01 in Malays, but absent in 984 Caucasian alleles and in the 1000 genomes project. In electrophysiological analyses, the variant decreased voltage-dependent inactivation, thus causing a gain of function of CaV1.2. We also observed a negative shift of V1/2 of activation and positive shift of V1/2 of channel inactivation, resulting in an increase of the window current. Together, these suggest a gain-of-function effect on CaV1.2 and suggest increased susceptibility for arrhythmias in certain clinical settings. The p.G1911R variant was also identified in a case of sudden unexplained infant death (SUID, for which an increasing number of clinical observations have demonstrated can be associated with arrhythmogenic mutations in cardiac ion channels. In summary, the combined effects of the CACNA1C variant to diminish voltage-dependent inactivation of CaV1.2 and increase window current expand our appreciation of mechanisms by which a gain of

  1. Voltage-Dependent Inhibition of Glycine Receptor Channels by Niflumic Acid

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    Galyna Maleeva

    2017-05-01

    Full Text Available Niflumic acid (NFA is a member of the fenamate class of nonsteroidal anti-inflammatory drugs. This compound and its derivatives are used worldwide clinically for the relief of chronic and acute pain. NFA is also a commonly used blocker of voltage-gated chloride channels. Here we present evidence that NFA is an efficient blocker of chloride-permeable glycine receptors (GlyRs with subunit heterogeneity of action. Using the whole-cell configuration of patch-clamp recordings and molecular modeling, we analyzed the action of NFA on homomeric α1ΔIns, α2B, α3L, and heteromeric α1β and α2β GlyRs expressed in CHO cells. NFA inhibited glycine-induced currents in a voltage-dependent manner and its blocking potency in α2 and α3 GlyRs was higher than that in α1 GlyR. The Woodhull analysis suggests that NFA blocks α1 and α2 GlyRs at the fractional electrical distances of 0.16 and 0.65 from the external membrane surface, respectively. Thus, NFA binding site in α1 GlyR is closer to the external part of the membrane, while in α2 GlyR it is significantly deeper in the pore. Mutation G254A at the cytoplasmic part of the α1 GlyR pore-lining TM2 helix (level 2′ increased the NFA blocking potency, while incorporation of the β subunit did not have a significant effect. The Hill plot analysis suggests that α1 and α2 GlyRs are preferably blocked by two and one NFA molecules, respectively. Molecular modeling using Monte Carlo energy minimizations provides the structural rationale for the experimental data and proposes more than one interaction site along the pore where NFA can suppress the ion permeation.

  2. Voltage-Dependent Inhibition of Glycine Receptor Channels by Niflumic Acid.

    Science.gov (United States)

    Maleeva, Galyna; Peiretti, Franck; Zhorov, Boris S; Bregestovski, Piotr

    2017-01-01

    Niflumic acid (NFA) is a member of the fenamate class of nonsteroidal anti-inflammatory drugs. This compound and its derivatives are used worldwide clinically for the relief of chronic and acute pain. NFA is also a commonly used blocker of voltage-gated chloride channels. Here we present evidence that NFA is an efficient blocker of chloride-permeable glycine receptors (GlyRs) with subunit heterogeneity of action. Using the whole-cell configuration of patch-clamp recordings and molecular modeling, we analyzed the action of NFA on homomeric α1ΔIns, α2B, α3L, and heteromeric α1β and α2β GlyRs expressed in CHO cells. NFA inhibited glycine-induced currents in a voltage-dependent manner and its blocking potency in α2 and α3 GlyRs was higher than that in α1 GlyR. The Woodhull analysis suggests that NFA blocks α1 and α2 GlyRs at the fractional electrical distances of 0.16 and 0.65 from the external membrane surface, respectively. Thus, NFA binding site in α1 GlyR is closer to the external part of the membrane, while in α2 GlyR it is significantly deeper in the pore. Mutation G254A at the cytoplasmic part of the α1 GlyR pore-lining TM2 helix (level 2') increased the NFA blocking potency, while incorporation of the β subunit did not have a significant effect. The Hill plot analysis suggests that α1 and α2 GlyRs are preferably blocked by two and one NFA molecules, respectively. Molecular modeling using Monte Carlo energy minimizations provides the structural rationale for the experimental data and proposes more than one interaction site along the pore where NFA can suppress the ion permeation.

  3. Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.

    Science.gov (United States)

    Liu, Dong-Hai; Huang, Xu; Guo, Xin; Meng, Xiang-Min; Wu, Yi-Song; Lu, Hong-Li; Zhang, Chun-Mei; Kim, Young-chul; Xu, Wen-Xie

    2014-01-01

    Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV) was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV) to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.

  4. Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.

    Directory of Open Access Journals (Sweden)

    Dong-Hai Liu

    Full Text Available Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.

  5. Voltage-Dependent Anion Channel-1, a Possible Ligand of Plasminogen Kringle 5.

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    Yin-Ku Liang

    Full Text Available Kringle 5, the fifth fragment of plasminogen, is known to be important for inhibiting the proliferation and migration of vascular endothelial cell (VEC, while not having any effects on normal endothelial cells. Therefore, it may be a potential tumor therapy candidate. However, the ligand of the Kringle 5 in VEC has not yet been identified. In this study, the possible ligand of Kringle 5 in vitro was screened and validated using Ph.D.-7 phage display peptide library with molecular docking, along with surface plasma resonance (SPR. After four rounds of panning, the specific clones of Kringle 5 were confirmed using enzyme-linked immunosorbent assay (ELISA. The gene sequence analysis showed that they expressed the common amino sequence IGNSNTL. Then, using a NCBI BLAST, 103 matching sequences were found. Following the molecular docking evaluation and considering the acting function and pathway of the plasminogen Kringle 5 in the human body, the most promising candidate was determined to be voltage-dependent anion channel-1 (VDAC-1, which was able to bind to Kringle 5 at -822.65 J·mol-1 of the binding energy at the residues of Lys12, Thr19, Ser57, Thr188, Arg139, Asn214, Ser240 and Lys274. A strong dose-dependent interaction occurred between the VDAC-1 and Kringle 5 (binding constant 2.43 × 103 L·mol-1 in SPR observation. Therefore, this study proposed that VDAC-1 was a potential ligand of plasminogen Kringle 5, and also demonstrated that the screening and validation of protein ligand using phage display peptide library with the molecular docking, along with SPR, was a practicable application.

  6. Voltage dependent anion channel-1 regulates death receptor mediated apoptosis by enabling cleavage of caspase-8

    International Nuclear Information System (INIS)

    Chacko, Alex D; Liberante, Fabio; Paul, Ian; Longley, Daniel B; Fennell, Dean A

    2010-01-01

    Activation of the extrinsic apoptosis pathway by tumour necrosis factor related apoptosis inducing ligand (TRAIL) is a novel therapeutic strategy for treating cancer that is currently under clinical evaluation. Identification of molecular biomarkers of resistance is likely to play an important role in predicting clinical anti tumour activity. The involvement of the mitochondrial type 1 voltage dependent anion channel (VDAC1) in regulating apoptosis has been highly debated. To date, a functional role in regulating the extrinsic apoptosis pathway has not been formally excluded. We carried out stable and transient RNAi knockdowns of VDAC1 in non-small cell lung cancer cells, and stimulated the extrinsic apoptotic pathway principally by incubating cells with the death ligand TRAIL. We used in-vitro apoptotic and cell viability assays, as well as western blot for markers of apoptosis, to demonstrate that TRAIL-induced toxicity is VDAC1 dependant. Confocal microscopy and mitochondrial fractionation were used to determine the importance of mitochondria for caspase-8 activation. Here we show that either stable or transient knockdown of VDAC1 is sufficient to antagonize TRAIL mediated apoptosis in non-small cell lung cancer (NSCLC) cells. Specifically, VDAC1 is required for processing of procaspase-8 to its fully active p18 form at the mitochondria. Loss of VDAC1 does not alter mitochondrial sensitivity to exogenous caspase-8-cleaved BID induced mitochondrial depolarization, even though VDAC1 expression is essential for TRAIL dependent activation of the intrinsic apoptosis pathway. Furthermore, expression of exogenous VDAC1 restores the apoptotic response to TRAIL in cells in which endogenous VDAC1 has been selectively silenced. Expression of VDAC1 is required for full processing and activation of caspase-8 and supports a role for mitochondria in regulating apoptosis signaling via the death receptor pathway

  7. Anatomical distribution of voltage-dependent membrane capacitance in frog skeletal muscle fibers.

    Science.gov (United States)

    Huang, C L; Peachey, L D

    1989-03-01

    Components of nonlinear capacitance, or charge movement, were localized in the membranes of frog skeletal muscle fibers by studying the effect of 'detubulation' resulting from sudden withdrawal of glycerol from a glycerol-hypertonic solution in which the muscles had been immersed. Linear capacitance was evaluated from the integral of the transient current elicited by imposed voltage clamp steps near the holding potential using bathing solutions that minimized tubular voltage attenuation. The dependence of linear membrane capacitance on fiber diameter in intact fibers was consistent with surface and tubular capacitances and a term attributable to the capacitance of the fiber end. A reduction in this dependence in detubulated fibers suggested that sudden glycerol withdrawal isolated between 75 and 100% of the transverse tubules from the fiber surface. Glycerol withdrawal in two stages did not cause appreciable detubulation. Such glycerol-treated but not detubulated fibers were used as controls. Detubulation reduced delayed (q gamma) charging currents to an extent not explicable simply in terms of tubular conduction delays. Nonlinear membrane capacitance measured at different voltages was expressed normalized to accessible linear fiber membrane capacitance. In control fibers it was strongly voltage dependent. Both the magnitude and steepness of the function were markedly reduced by adding tetracaine, which removed a component in agreement with earlier reports for q gamma charge. In contrast, detubulated fibers had nonlinear capacitances resembling those of q beta charge, and were not affected by adding tetracaine. These findings are discussed in terms of a preferential localization of tetracaine-sensitive (q gamma) charge in transverse tubule membrane, in contrast to a more even distribution of the tetracaine-resistant (q beta) charge in both transverse tubule and surface membranes. These results suggest that q beta and q gamma are due to different molecules and that

  8. Monitoring voltage-dependent charge displacement of Shaker B-IR K+ ion channels using radio frequency interrogation.

    Directory of Open Access Journals (Sweden)

    Sameera Dharia

    2011-02-01

    Full Text Available Here we introduce a new technique that probes voltage-dependent charge displacements of excitable membrane-bound proteins using extracellularly applied radio frequency (RF, 500 kHz electric fields. Xenopus oocytes were used as a model cell for these experiments, and were injected with cRNA encoding Shaker B-IR (ShB-IR K(+ ion channels to express large densities of this protein in the oocyte membranes. Two-electrode voltage clamp (TEVC was applied to command whole-cell membrane potential and to measure channel-dependent membrane currents. Simultaneously, RF electric fields were applied to perturb the membrane potential about the TEVC level and to measure voltage-dependent RF displacement currents. ShB-IR expressing oocytes showed significantly larger changes in RF displacement currents upon membrane depolarization than control oocytes. Voltage-dependent changes in RF displacement currents further increased in ShB-IR expressing oocytes after ∼120 µM Cu(2+ addition to the external bath. Cu(2+ is known to bind to the ShB-IR ion channel and inhibit Shaker K(+ conductance, indicating that changes in the RF displacement current reported here were associated with RF vibration of the Cu(2+-linked mobile domain of the ShB-IR protein. Results demonstrate the use of extracellular RF electrodes to interrogate voltage-dependent movement of charged mobile protein domains--capabilities that might enable detection of small changes in charge distribution associated with integral membrane protein conformation and/or drug-protein interactions.

  9. Monitoring voltage-dependent charge displacement of Shaker B-IR K+ ion channels using radio frequency interrogation.

    Science.gov (United States)

    Dharia, Sameera; Rabbitt, Richard D

    2011-02-28

    Here we introduce a new technique that probes voltage-dependent charge displacements of excitable membrane-bound proteins using extracellularly applied radio frequency (RF, 500 kHz) electric fields. Xenopus oocytes were used as a model cell for these experiments, and were injected with cRNA encoding Shaker B-IR (ShB-IR) K(+) ion channels to express large densities of this protein in the oocyte membranes. Two-electrode voltage clamp (TEVC) was applied to command whole-cell membrane potential and to measure channel-dependent membrane currents. Simultaneously, RF electric fields were applied to perturb the membrane potential about the TEVC level and to measure voltage-dependent RF displacement currents. ShB-IR expressing oocytes showed significantly larger changes in RF displacement currents upon membrane depolarization than control oocytes. Voltage-dependent changes in RF displacement currents further increased in ShB-IR expressing oocytes after ∼120 µM Cu(2+) addition to the external bath. Cu(2+) is known to bind to the ShB-IR ion channel and inhibit Shaker K(+) conductance, indicating that changes in the RF displacement current reported here were associated with RF vibration of the Cu(2+)-linked mobile domain of the ShB-IR protein. Results demonstrate the use of extracellular RF electrodes to interrogate voltage-dependent movement of charged mobile protein domains--capabilities that might enable detection of small changes in charge distribution associated with integral membrane protein conformation and/or drug-protein interactions.

  10. NO involvement in the inhibition of ghrelin on voltage-dependent potassium currents in rat hippocampal cells.

    Science.gov (United States)

    Lu, Yong; Dang, Shaokang; Wang, Xu; Zhang, Junli; Zhang, Lin; Su, Qian; Zhang, Huiping; Lin, Tianwei; Zhang, Xiaoxiao; Zhang, Yurong; Sun, Hongli; Zhu, Zhongliang; Li, Hui

    2018-01-01

    Ghrelin is a peptide hormone that plays an important role in promoting appetite, regulating distribution and rate of use of energy, cognition, and mood disorders, but the relevant neural mechanisms of these function are still not clear. In this study, we examined the effect of ghrelin on voltage-dependent potassium (K + ) currents in hippocampal cells of 1-3 days SD rats by whole-cell patch-clamp technique, and discussed whether NO was involved in this process. The results showed that ghrelin significantly inhibited the voltage-dependent K + currents in hippocampal cells, and the inhibitory effect was more significant when l-arginine was co-administered. In contrast, N-nitro- l-arginine methyl ester increased the ghrelin inhibited K + currents and attenuated the inhibitory effect of ghrelin. While d-arginine (D-AA) showed no significant impact on the ghrelin-induced decrease in K + current. These results show that ghrelin may play a physiological role by inhibiting hippocampal voltage dependent K + currents, and the NO pathway may be involved in this process. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Direct modulation of the outer mitochondrial membrane channel, voltage-dependent anion channel 1 (VDAC1) by cannabidiol: a novel mechanism for cannabinoid-induced cell death.

    Science.gov (United States)

    Rimmerman, N; Ben-Hail, D; Porat, Z; Juknat, A; Kozela, E; Daniels, M P; Connelly, P S; Leishman, E; Bradshaw, H B; Shoshan-Barmatz, V; Vogel, Z

    2013-12-05

    Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that inhibits cell proliferation and induces cell death of cancer cells and activated immune cells. It is not an agonist of the classical CB1/CB2 cannabinoid receptors and the mechanism by which it functions is unknown. Here, we studied the effects of CBD on various mitochondrial functions in BV-2 microglial cells. Our findings indicate that CBD treatment leads to a biphasic increase in intracellular calcium levels and to changes in mitochondrial function and morphology leading to cell death. Density gradient fractionation analysis by mass spectrometry and western blotting showed colocalization of CBD with protein markers of mitochondria. Single-channel recordings of the outer-mitochondrial membrane protein, the voltage-dependent anion channel 1 (VDAC1) functioning in cell energy, metabolic homeostasis and apoptosis revealed that CBD markedly decreases channel conductance. Finally, using microscale thermophoresis, we showed a direct interaction between purified fluorescently labeled VDAC1 and CBD. Thus, VDAC1 seems to serve as a novel mitochondrial target for CBD. The inhibition of VDAC1 by CBD may be responsible for the immunosuppressive and anticancer effects of CBD.

  12. Monitoring Voltage-Dependent Charge Displacement of Shaker B-IR K+ Ion Channels Using Radio Frequency Interrogation

    OpenAIRE

    Dharia, Sameera; Rabbitt, Richard D.

    2011-01-01

    Here we introduce a new technique that probes voltage-dependent charge displacements of excitable membrane-bound proteins using extracellularly applied radio frequency (RF, 500 kHz) electric fields. Xenopus oocytes were used as a model cell for these experiments, and were injected with cRNA encoding Shaker B-IR (ShB-IR) K(+) ion channels to express large densities of this protein in the oocyte membranes. Two-electrode voltage clamp (TEVC) was applied to command whole-cell membrane potential a...

  13. The human red cell voltage-dependent cation channel. Part III: Distribution homogeneity and pH dependence

    DEFF Research Database (Denmark)

    Bennekou, P.; Barksmann, T. L.; Christophersen, P.

    2006-01-01

    The homogeneity of the distribution of the non-selective voltage-dependent cation channel (the NSVDC channel) in the human erythrocyte, and the pH dependence was investigated. Activation of this channel caused a uniform cellular dehydration, which was characterized by the changes in the erythrocy...... - but not the extracellular - pH. The apparent pKA value for the effect was estimated to be 6.5, and the specific histidine reagent 2.4'-dibromoacetophenone (DBAB) inactivated the NSVDC channel....

  14. Breakdown voltage mapping through voltage dependent ReBEL intensity imaging of multi-crystalline Si solar cells

    Science.gov (United States)

    Dix-Peek, RM.; van Dyk, EE.; Vorster, FJ.; Pretorius, CJ.

    2018-04-01

    Device material quality affects both the efficiency and the longevity of photovoltaic (PV) cells. Therefore, identifying these defects can be beneficial in the development of more efficient and longer lasting PV cells. In this study, a combination of spatially-resolved, electroluminescence (EL), and light beam induced current (LBIC) measurements, were used to identify specific defects and features of a multi-crystalline Si PV cells. In this study, a novel approach is used to map the breakdown voltage of a PV cell through voltage dependent Reverse Bias EL (ReBEL) intensity imaging.

  15. Frequency and voltage dependent electrical responses of poly(triarylamine) thin film-based organic Schottky diode

    Science.gov (United States)

    Anuar Mohamad, Khairul; Tak Hoh, Hang; Alias, Afishah; Ghosh, Bablu Kumar; Fukuda, Hisashi

    2017-11-01

    A metal-organic-metal (MOM) type Schottky diode based on poly (triarylamine) (PTAA) thin films has been fabricated by using the spin coating method. Investigation of the frequency dependent conductance-voltage (G-V-f) and capacitance-voltage (C-V-f) characteristics of the ITO/PTAA/Al MOM type diode were carried out in the frequency range from 12 Hz to 100 kHz using an LCR meter at room temperature. The frequency and bias voltage dependent electrical response were determined by admittance-based measured method in terms of an equivalent circuit model of the parallel combination of resistance and capacitance (RC circuit). Investigation revealed that the conductance is frequency and a bias voltage dependent in which conductance continuous increase as the increasing frequency, respectively. Meanwhile, the capacitance is dependent on frequency up to a certain value of frequency (100 Hz) but decreases at high frequency (1 - 10 kHz). The interface state density in the Schottky diode was determined from G-V and C-V characteristics. The interface state density has values almost constant of 2.8 x 1012 eV-1cm-2 with slightly decrease by increasing frequencies. Consequently, both series resistance and interface trap density were found to decrease with increasing frequency. The frequency dependence of the electrical responses is attributed the distribution density of interface states that could follow the alternating current (AC) signal.

  16. Frequency and voltage dependent electrical responses of poly(triarylamine thin film-based organic Schottky diode

    Directory of Open Access Journals (Sweden)

    Mohamad Khairul Anuar

    2017-01-01

    Full Text Available A metal-organic-metal (MOM type Schottky diode based on poly (triarylamine (PTAA thin films has been fabricated by using the spin coating method. Investigation of the frequency dependent conductance-voltage (G-V-f and capacitance-voltage (C-V-f characteristics of the ITO/PTAA/Al MOM type diode were carried out in the frequency range from 12 Hz to 100 kHz using an LCR meter at room temperature. The frequency and bias voltage dependent electrical response were determined by admittance-based measured method in terms of an equivalent circuit model of the parallel combination of resistance and capacitance (RC circuit. Investigation revealed that the conductance is frequency and a bias voltage dependent in which conductance continuous increase as the increasing frequency, respectively. Meanwhile, the capacitance is dependent on frequency up to a certain value of frequency (100 Hz but decreases at high frequency (1 – 10 kHz. The interface state density in the Schottky diode was determined from G-V and C-V characteristics. The interface state density has values almost constant of 2.8 x 1012 eV−1cm−2 with slightly decrease by increasing frequencies. Consequently, both series resistance and interface trap density were found to decrease with increasing frequency. The frequency dependence of the electrical responses is attributed the distribution density of interface states that could follow the alternating current (AC signal.

  17. Voltage dependence of intramembrane charge movement and conductance activation of batrachotoxin-modified sodium channels in frog node of Ranvier

    Science.gov (United States)

    1983-01-01

    Sodium current and sodium channel intramembrane gating charge movement (Q) were monitored in voltage-clamped frog node of Ranvier after modification of all sodium channels by batrachotoxin (BTX). BTX caused an approximately threefold increase in steepness of the Q vs. voltage relationship and a 50-mV negative shift in its midpoint. The maximum amount of intramembrane charge was virtually identical before and after BTX treatment. BTX treatment eliminated the charge immobilization observed in untreated nodes after relatively long depolarizing pulses and slowed the rate of OFF charge movement after a pulse. After BTX treatment, the voltage dependence of charge movement was the same as the steady-state voltage dependence of sodium conductance activation. The observations are consistent with the hypothesis that BTX induces an aggregation of the charged gating particles associated with each channel and causes them to move as a unit having approximately three times the average valence of the individual particles. Movement of this single aggregated unit would open the BTX-modified sodium channel. PMID:6308127

  18. Functional coupling between sodium-activated potassium channels and voltage-dependent persistent sodium currents in cricket Kenyon cells.

    Science.gov (United States)

    Takahashi, Izumi; Yoshino, Masami

    2015-10-01

    In this study, we examined the functional coupling between Na(+)-activated potassium (KNa) channels and Na(+) influx through voltage-dependent Na(+) channels in Kenyon cells isolated from the mushroom body of the cricket Gryllus bimaculatus. Single-channel activity of KNa channels was recorded with the cell-attached patch configuration. The open probability (Po) of KNa channels increased with increasing Na(+) concentration in a bath solution, whereas it decreased by the substitution of Na(+) with an equimolar concentration of Li(+). The Po of KNa channels was also found to be reduced by bath application of a high concentration of TTX (1 μM) and riluzole (100 μM), which inhibits both fast (INaf) and persistent (INaP) Na(+) currents, whereas it was unaffected by a low concentration of TTX (10 nM), which selectively blocks INaf. Bath application of Cd(2+) at a low concentration (50 μM), as an inhibitor of INaP, also decreased the Po of KNa channels. Conversely, bath application of the inorganic Ca(2+)-channel blockers Co(2+) and Ni(2+) at high concentrations (500 μM) had little effect on the Po of KNa channels, although Cd(2+) (500 μM) reduced the Po of KNa channels. Perforated whole cell clamp analysis further indicated the presence of sustained outward currents for which amplitude was dependent on the amount of Na(+) influx. Taken together, these results indicate that KNa channels could be activated by Na(+) influx passing through voltage-dependent persistent Na(+) channels. The functional significance of this coupling mechanism was discussed in relation to the membrane excitability of Kenyon cells and its possible role in the formation of long-term memory. Copyright © 2015 the American Physiological Society.

  19. trans-Caryophyllene, a Natural Sesquiterpene, Causes Tracheal Smooth Muscle Relaxation through Blockade of Voltage-Dependent Ca2+ Channels

    Directory of Open Access Journals (Sweden)

    Jader Santos Cruz

    2012-10-01

    Full Text Available trans-Caryophyllene is a major component in the essential oils of various species of medicinal plants used in popular medicine in Brazil. It belongs to the chemical class of the sesquiterpenes and has been the subject of a number of studies. Here, we evaluated the effects of this compound in airway smooth muscle. The biological activities of trans-caryophyllene were examined in isolated bath organs to investigate the effect in basal tonus. Electromechanical and pharmacomechanical couplings were evaluated through the responses to K+ depolarization and exposure to acetylcholine (ACh, respectively. Isolated cells of rat tracheal smooth muscle were used to investigate trans-caryophyllene effects on voltage-dependent Ca2+ channels by using the whole-cell voltage-clamp configuration of the patch-clamp technique. trans-Caryophyllene showed more efficiency in the blockade of electromechanical excitation-contraction coupling while it has only minor inhibitory effect on pharmacomechanical coupling. Epithelium removal does not modify tracheal smooth muscle response elicited by trans-caryophyllene in the pharmacomechanical coupling. Under Ca2+-free conditions, pre-exposure to trans-caryophyllene did not reduce the contraction induced by ACh in isolated rat tracheal smooth muscle, regardless of the presence of intact epithelium. In the whole-cell configuration, trans-caryophyllene (3 mM, inhibited the inward Ba2+ current (IBa to approximately 50% of control levels. Altogether, our results demonstrate that trans-caryophyllene has anti-spasmodic activity on rat tracheal smooth muscle which could be explained, at least in part, by the voltage-dependent Ca2+ channels blockade.

  20. Voltage-dependent antagonist/agonist actions of taurine on Ca(2+)-activated potassium channels of rat skeletal muscle fibers.

    Science.gov (United States)

    Tricarico, D; Barbieri, M; Conte Camerino, D

    2001-09-01

    Emerging evidence supports the idea that taurine exerts some of its actions through inhibition of inward rectifier K(+) channels, ATP-sensitive K(+) channels, and voltage-dependent K(+) channels. However, to date not much is known about the effects of this sulfonic amino acid on Ca(2+)-activated K(+) (K(Ca(2+))) channels, which are widely expressed in various tissues, including skeletal muscle. In the present work, the effects of taurine on K(Ca(2+)) channels of rat skeletal muscle fibers were investigated using the patch-clamp technique. The application of the amino acid to the internal side of the excised macropatches induced a dose-dependent decrease in the outward K(Ca(2+)) currents recorded at positive membrane potentials in the presence of 8 to 16 microM concentrations of free Ca(2+) ions in the bath with an IC(50) of 31.9. 10(-3) +/- 1 M (slope factor = 1.2) (n = 11 patches). In contrast, at negative membrane potentials taurine caused an enhancement of the muscular inward K(Ca(2+)) currents with a DE(50) (drug concentration needed to enhance the current by 50%) of 46.7. 10(-3) +/- 2 M (slope factor = 1.3) (n = 9 patches). Single channel analysis revealed that this effect was mediated by changes in the reversal potential of the K(Ca(2+)) channel for K(+) ions with no changes in the gating properties or in the sensitivity of the channel to Ca(2+) ions. Taurine also did not affect the single channel conductance. In conclusion, taurine shows a voltage-dependent dualistic action on K(Ca(2+)) channels, being an inhibitor of the channel at positive membrane potentials and an activator at negative membrane potentials.

  1. The voltage-dependent K+ channels Kv1.3 and Kv1.5 in human cancer

    Directory of Open Access Journals (Sweden)

    Núria eComes

    2013-10-01

    Full Text Available Voltage-dependent K+ channels (Kv are involved in a number of physiological processes, including immunomodulation, cell volume regulation, apoptosis as well as differentiation. Some Kv channels participate in the proliferation and migration of normal and tumour cells, contributing to metastasis. Altered expression of Kv1.3 and Kv1.5 channels has been found in several types of tumours and cancer cells. In general, while the expression of Kv1.3 apparently exhibits no clear pattern, Kv1.5 is induced in many of the analyzed metastatic tissues. Interestingly, evidence indicates that Kv1.5 channel shows inversed correlation with malignancy in some gliomas and non-Hodgkin’s lymphomas. However, Kv1.3 and Kv1.5 are similarly remodelled in some cancers. For instance, expression of Kv1.3 and Kv1.5 correlates with a certain grade of tumorigenicity in muscle sarcomas. Differential remodelling of Kv1.3 and Kv1.5 expression in human cancers may indicate their role in tumour growth and their importance as potential tumour markers. However, despite of this increasing body of information, which considers Kv1.3 and Kv1.5 as emerging tumoral markers, further research must be performed to reach any conclusion. In this review, we summarize what it has been lately documented about Kv1.3 and Kv1.5 channels in human cancer.

  2. Bias-voltage dependent ultraviolet photodetectors prepared by GaOx + ZnO mixture phase nanocrystalline thin films

    International Nuclear Information System (INIS)

    Wang, Rongxin; Yang, Lechen; Xu, Shijie; Zhang, Xiaodong; Dong, Xue; Zhao, Yingchun; Fu, Kai; Zhang, Baoshun; Yang, Hui

    2013-01-01

    Highlights: •GaO x + ZnO thin films sputtered and annealed exhibit interesting and unique optical properties, especially deep UV photo response. •GaO x + ZnO thin films can be used to fabricate efficient deep UV photodetectors. •The mixture phase nature of GaO x + ZnO thin films is revealed to be responsible for the unique characteristics of the photodetectors. •Two bands in UV range can be adjusted by a applied voltage when the PDs were fabricated using the mixture phase nature of GaO x + ZnO thin films. -- Abstract: Ultraviolet (UV) photodetectors were prepared by using the GaO x + ZnO mixture phase thin films sputtered on sapphire as the photoresponse layer. The devices show good photoresponse in UV range. More interestingly, the device responsivity in the wavelength less than 280 nm range rapidly increases with increasing the applied voltage and becomes dominant for the bias ⩾3.0 V. X-ray diffraction, absorption and cathodoluminescence measurements firmly reveal the mixture phases in the thin films. Electric field dependent detrapping of photo-excited carriers in nanocrystals in the films shall be responsible for the observed bias-voltage dependent deep UV photoresponse of the devices

  3. Increased voltage-dependent K+ channel Kv1.3 and Kv1.5 expression correlates with leiomyosarcoma aggressiveness

    Science.gov (United States)

    BIELANSKA, JOANNA; HERNÁNDEZ-LOSA, JAVIER; MOLINE, TERESA; SOMOZA, ROSA; RAMÓN Y CAJAL, SANTIAGO; CONDOM, ENRIC; FERRERES, JOAN CARLES; FELIPE, ANTONIO

    2012-01-01

    Voltage-dependent K+ channels (Kv) are involved in the proliferation and differentiation of mammalian cells, since Kv antagonists impair cell cycle progression. Although myofibers are terminally differentiated, some myoblasts may re-enter the cell cycle and proliferate. Since Kv1.3 and Kv1.5 expression is remodeled during tumorigenesis and is involved in smooth muscle proliferation, the purpose of this study was to analyze the expression of Kv1.3 and Kv1.5 in smooth muscle neoplasms. In the present study, we examined human samples of smooth muscle tumors together with healthy specimens. Thus, leiomyoma (LM) and leiomyosarcoma (LMS) tumors were analyzed. Results showed that Kv1.3 was poorly expressed in the healthy muscle and indolent LM specimens, whereas aggressive LMS showed high levels of Kv1.3 expression. Kv1.5 staining was correlated with malignancy. The findings show a remodeling of Kv1.3 and Kv1.5 in human smooth muscle sarcoma. A correlation of Kv1.3 and Kv1.5 expression with tumor aggressiveness was observed. Thus, our results indicate Kv1.5 and Kv1.3 as potential tumorigenic targets for aggressive human LMS. PMID:22844358

  4. Two separate interfaces between the voltage sensor and pore are required for the function of voltage-dependent K(+ channels.

    Directory of Open Access Journals (Sweden)

    Seok-Yong Lee

    2009-03-01

    Full Text Available Voltage-dependent K(+ (Kv channels gate open in response to the membrane voltage. To further our understanding of how cell membrane voltage regulates the opening of a Kv channel, we have studied the protein interfaces that attach the voltage-sensor domains to the pore. In the crystal structure, three physical interfaces exist. Only two of these consist of amino acids that are co-evolved across the interface between voltage sensor and pore according to statistical coupling analysis of 360 Kv channel sequences. A first co-evolved interface is formed by the S4-S5 linkers (one from each of four voltage sensors, which form a cuff surrounding the S6-lined pore opening at the intracellular surface. The crystal structure and published mutational studies support the hypothesis that the S4-S5 linkers convert voltage-sensor motions directly into gate opening and closing. A second co-evolved interface forms a small contact surface between S1 of the voltage sensor and the pore helix near the extracellular surface. We demonstrate through mutagenesis that this interface is necessary for the function and/or structure of two different Kv channels. This second interface is well positioned to act as a second anchor point between the voltage sensor and the pore, thus allowing efficient transmission of conformational changes to the pore's gate.

  5. Evolution of Voltage-Dependent Anion Channel Function: From Molecular Sieve to Governator to Actuator of Ferroptosis

    Directory of Open Access Journals (Sweden)

    John J. Lemasters

    2017-12-01

    Full Text Available The voltage-dependent anion channel (VDAC is well known as the pathway for passive diffusion of anionic hydrophilic mitochondrial metabolites across the outer membrane, but a more complex functionality of the three isoforms of VDAC has emerged, as addressed in the Frontiers in Oncology Research Topic on “Uncovering the Function of the Mitochondrial Protein VDAC in Health and Disease: from Structure-Function to Novel Therapeutic Strategies.” VDAC as the single most abundant protein in mitochondrial outer membranes is typically involved in isoform-specific interactions of the mitochondrion with its surroundings as, for example, during mitochondria-dependent pathways of cell death. VDAC closure can also act as an adjustable limiter (governator of global mitochondrial metabolism, as during hepatic ethanol metabolism to promote selective oxidation of membrane-permeant acetaldehyde. In cancer cells, high free tubulin inhibits VDAC1 and VDAC2, contributing to suppression of mitochondrial function in the Warburg phenomenon. Erastin, the canonical inducer of ferroptosis, opens VDAC in the presence of tubulin and hyperpolarizes mitochondria, leading to mitochondrial production of reactive oxygen species, mitochondrial dysfunction, and cell death. Our understanding of VDAC function continues to evolve.

  6. Augmented norepinephrine-stimulated Ca2+ entry via voltage-dependent Ca2+ channels in spontaneously hypertensive rats (SHR): effects of captopril treatment

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Dobešová, Zdenka; Paulis, L.; Kuneš, Jaroslav

    2006-01-01

    Roč. 22, č. 13 (2006), s. 58-58 ISSN 1000-4718. [International Congress of Pathophysiology /5./. 28.06.2006-01.07.2006, Beijing] R&D Projects: GA MZd(CZ) NR7786 Keywords : Ca2+ entry * voltage-dependent Ca2+ channels * hypertensive rat Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  7. Lack of negatively charged residues at the external mouth of Kir2.2 channels enable the voltage-dependent block by external Mg2+.

    Directory of Open Access Journals (Sweden)

    Junwei Li

    Full Text Available Kir channels display voltage-dependent block by cytosolic cations such as Mg2+ and polyamines that causes inward rectification. In fact, cations can regulate K channel activity from both the extracellular and intracellular sides. Previous studies have provided insight into the up-regulation of Kir channel activity by extracellular K+ concentration. In contrast, extracellular Mg2+ has been found to reduce the amplitude of the single-channel current at milimolar concentrations. However, little is known about the molecular mechanism of Kir channel blockade by external Mg2+ and the relationship between the Mg2+ blockade and activity potentiation by permeant K+ ions. In this study, we applied an interactive approach between theory and experiment. Electrophysiological recordings on Kir2.2 and its mutants were performed by heterologous expression in Xenopus laevis oocytes. Our results confirmed that extracellular Mg2+ could reduce heterologously expressed WT Kir2.2 currents in a voltage dependent manner. The kinetics of inhibition and recovery of Mg2+ exhibit a 3∼4s time constant. Molecular dynamics simulation results revealed a Mg2+ binding site located at the extracellular mouth of Kir2.2 that showed voltage-dependent Mg2+ binding. The mutants, G119D, Q126E and H128D, increased the number of permeant K+ ions and reduced the voltage-dependent blockade of Kir2.2 by extracellular Mg2+.

  8. Opening of voltage dependent anion channels promotes reactive oxygen species generation, mitochondrial dysfunction and cell death in cancer cells.

    Science.gov (United States)

    DeHart, David N; Fang, Diana; Heslop, Kareem; Li, Li; Lemasters, John J; Maldonado, Eduardo N

    2018-02-01

    Enhancement of aerobic glycolysis and suppression of mitochondrial metabolism characterize the pro-proliferative Warburg phenotype of cancer cells. High free tubulin in cancer cells closes voltage dependent anion channels (VDAC) to decrease mitochondrial membrane potential (ΔΨ), an effect antagonized by erastin, the canonical promotor of ferroptosis. Previously, we identified six compounds (X1-X6) that also block tubulin-dependent mitochondrial depolarization. Here, we hypothesized that VDAC opening after erastin and X1-X6 increases mitochondrial metabolism and reactive oxygen species (ROS) formation, leading to ROS-dependent mitochondrial dysfunction, bioenergetic failure and cell death. Accordingly, we characterized erastin and the two most potent structurally unrelated lead compounds, X1 and X4, on ROS formation, mitochondrial function and cell viability. Erastin, X1 and X4 increased ΔΨ followed closely by an increase in mitochondrial ROS generation within 30-60 min. Subsequently, mitochondria began to depolarize after an hour or longer indicative of mitochondrial dysfunction. N-acetylcysteine (NAC, glutathione precursor and ROS scavenger) and MitoQ (mitochondrially targeted antioxidant) blocked increased ROS formation after X1 and prevented mitochondrial dysfunction. Erastin, X1 and X4 selectively promoted cell killing in HepG2 and Huh7 human hepatocarcinoma cells compared to primary rat hepatocytes. X1 and X4-dependent cell death was blocked by NAC. These results suggest that ferroptosis induced by erastin and our erastin-like lead compounds was caused by VDAC opening, leading to increased ΔΨ, mitochondrial ROS generation and oxidative stress-induced cell death. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Immunomodulatory effects of diclofenac in leukocytes through the targeting of Kv1.3 voltage-dependent potassium channels.

    Science.gov (United States)

    Villalonga, Núria; David, Miren; Bielańska, Joanna; González, Teresa; Parra, David; Soler, Concepció; Comes, Núria; Valenzuela, Carmen; Felipe, Antonio

    2010-09-15

    Kv1.3 plays a crucial role in the activation and proliferation of T-lymphocytes and macrophages. While Kv1.3 is responsible for the voltage-dependent potassium current in T-cells, in macrophages this K(+) current is generated by the association of Kv1.3 and Kv1.5. Patients with autoimmune diseases show a high number of effector memory T cells that are characterized by a high expression of Kv1.3 and Kv1.3 antagonists ameliorate autoimmune disorders in vivo. Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) used in patients who suffer from painful autoimmune diseases such as rheumatoid arthritis. In this study, we show that diclofenac impairs immune response via a mechanism that involves Kv1.3. While diclofenac inhibited Kv1.3 expression in activated macrophages and T-lymphocytes, Kv1.5 remained unaffected. Diclofenac also decreased iNOS levels in Raw 264.7 cells, impairing their activation in response to lipopolysaccharide (LPS). LPS-induced macrophage migration and IL-2 production in stimulated Jurkat T-cells were also blocked by pharmacological doses of diclofenac. These effects were mimicked by Margatoxin, a specific Kv1.3 inhibitor, and Charybdotoxin, which blocks both Kv1.3 and Ca(2+)-activated K(+) channels (K(Ca)3.1). Because Kv1.3 is a very good target for autoimmune therapies, the effects of diclofenac on Kv1.3 are of high pharmacological relevance. Copyright 2010 Elsevier Inc. All rights reserved.

  10. Photoaffinity labeling with cholesterol analogues precisely maps a cholesterol-binding site in voltage-dependent anion channel-1.

    Science.gov (United States)

    Budelier, Melissa M; Cheng, Wayland W L; Bergdoll, Lucie; Chen, Zi-Wei; Janetka, James W; Abramson, Jeff; Krishnan, Kathiresan; Mydock-McGrane, Laurel; Covey, Douglas F; Whitelegge, Julian P; Evers, Alex S

    2017-06-02

    Voltage-dependent anion channel-1 (VDAC1) is a highly regulated β-barrel membrane protein that mediates transport of ions and metabolites between the mitochondria and cytosol of the cell. VDAC1 co-purifies with cholesterol and is functionally regulated by cholesterol, among other endogenous lipids. Molecular modeling studies based on NMR observations have suggested five cholesterol-binding sites in VDAC1, but direct experimental evidence for these sites is lacking. Here, to determine the sites of cholesterol binding, we photolabeled purified mouse VDAC1 (mVDAC1) with photoactivatable cholesterol analogues and analyzed the photolabeled sites with both top-down mass spectrometry (MS), and bottom-up MS paired with a clickable, stable isotope-labeled tag, FLI -tag. Using cholesterol analogues with a diazirine in either the 7 position of the steroid ring (LKM38) or the aliphatic tail (KK174), we mapped a binding pocket in mVDAC1 localized to Thr 83 and Glu 73 , respectively. When Glu 73 was mutated to a glutamine, KK174 no longer photolabeled this residue, but instead labeled the nearby Tyr 62 within this same binding pocket. The combination of analytical strategies employed in this work permits detailed molecular mapping of a cholesterol-binding site in a protein, including an orientation of the sterol within the site. Our work raises the interesting possibility that cholesterol-mediated regulation of VDAC1 may be facilitated through a specific binding site at the functionally important Glu 73 residue. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Effect of batrachotoxin on the electroplax of electric eel: evidence for voltage-dependent interaction with sodium channels.

    Science.gov (United States)

    Bartels-Bernal, E; Rosenberry, T L; Daly, J W

    1977-03-01

    Batrachotoxin under certain conditions has a strong depolarizing effect on the innervated membrane of the monocellular electroplax preparation from the electric eel, El-ectrophorus electricus. No effect is observed when the toxin (50-200 nM) is applied to the resting membrane for periods up to 1 hr. However, if the membrane is exposed to batrachotoxin and the cell is subjected to stimulation at a stimulus voltage slightly above the threshold for action potential firing, a progressive prolongation of the action potential and concomitant progressive depolarization of the innervated membrane is observed. When the membrane is depolarized by 15-20 mV, a further abrupt all-or-none depolarization occurs, and the potential attains a steady-state value between 0 and -10 mV. Brief stimulation of a cell in the presence of batrachotoxin is sufficient to define a batrachotoxin-treated cell, even though negligible depolarization occurs. If depolarizing agents such as carbamoylcholine or potassium chloride are introduced to such a cell in concentrations that normally produce a 20-30 mV depolarization, the abrupt all-or-none depolarization immediately occurs. All-or-none depolarizations arising from either electrical stimulation or depolarizing agents are unaffected by d-tubocurarine but are completely reversed by tetrodotoxin. Batrachotoxin thus appears to activate only the action potential sodium channels. In the batrachotoxin-treated membrane, these channels can attain stable steady states in either a closed configuration at the normal resting potential or in an open configuration after complete depolarization. A striking hysteresis cycle thus can be generated, which is strongly indicative of a voltage-dependent interaction of the toxin with the action potential sodium channels.

  12. Mild Alkalization Acutely Triggers the Warburg Effect by Enhancing Hexokinase Activity via Voltage-Dependent Anion Channel Binding.

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    Cung Hoa Thien Quach

    Full Text Available To fully understand the glycolytic behavior of cancer cells, it is important to recognize how it is linked to pH dynamics. Here, we evaluated the acute effects of mild acidification and alkalization on cancer cell glucose uptake and glycolytic flux and investigated the role of hexokinase (HK. Cancer cells exposed to buffers with graded pH were measured for 18F-fluorodeoxyglucose (FDG uptake, lactate production and HK activity. Subcellular localization of HK protein was assessed by western blots and confocal microscopy. The interior of T47D breast cancer cells was mildly alkalized to pH 7.5 by a buffer pH of 7.8, and this was accompanied by rapid increases of FDG uptake and lactate extrusion. This shift toward glycolytic flux led to the prompt recovery of a reversed pH gradient. In contrast, mild acidification rapidly reduced cellular FDG uptake and lactate production. Mild acidification decreased and mild alkalization increased mitochondrial HK translocation and enzyme activity. Cells transfected with specific siRNA against HK-1, HK-2 and voltage-dependent anion channel (VDAC1 displayed significant attenuation of pH-induced changes in FDG uptake. Confocal microscopy showed increased co-localization of HK-1 and HK-2 with VDAC1 by alkaline treatment. In isolated mitochondria, acidic pH increased and alkaline pH decreased release of free HK-1 and HK-2 from the mitochondrial pellet into the supernatant. Furthermore, experiments using purified proteins showed that alkaline pH promoted co-immunoprecipitation of HK with VDAC protein. These findings demonstrate that mild alkalization is sufficient to acutely trigger cancer cell glycolytic flux through enhanced activity of HK by promoting its mitochondrial translocation and VDAC binding. This process might serve as a mechanism through which cancer cells trigger the Warburg effect to maintain a dysregulated pH.

  13. Biophysical and Pharmacological Characterization of Nav1.9 Voltage Dependent Sodium Channels Stably Expressed in HEK-293 Cells.

    Directory of Open Access Journals (Sweden)

    Zhixin Lin

    Full Text Available The voltage dependent sodium channel Nav1.9, is expressed preferentially in peripheral sensory neurons and has been linked to human genetic pain disorders, which makes it target of interest for the development of new pain therapeutics. However, characterization of Nav1.9 pharmacology has been limited due in part to the historical difficulty of functionally expressing recombinant channels. Here we report the successful generation and characterization of human, mouse and rat Nav1.9 stably expressed in human HEK-293 cells. These cells exhibit slowly activating and inactivating inward sodium channel currents that have characteristics of native Nav1.9. Optimal functional expression was achieved by coexpression of Nav1.9 with β1/β2 subunits. While recombinantly expressed Nav1.9 was found to be sensitive to sodium channel inhibitors TC-N 1752 and tetracaine, potency was up to 100-fold less than reported for other Nav channel subtypes despite evidence to support an interaction with the canonical local anesthetic (LA binding region on Domain 4 S6. Nav1.9 Domain 2 S6 pore domain contains a unique lysine residue (K799 which is predicted to be spatially near the local anesthetic interaction site. Mutation of this residue to the consensus asparagine (K799N resulted in an increase in potency for tetracaine, but a decrease for TC-N 1752, suggesting that this residue can influence interaction of inhibitors with the Nav1.9 pore. In summary, we have shown that stable functional expression of Nav1.9 in the widely used HEK-293 cells is possible, which opens up opportunities to better understand channel properties and may potentially aid identification of novel Nav1.9 based pharmacotherapies.

  14. Distinct myocardial mechanisms underlie cardiac dysfunction in endotoxemic male and female mice

    OpenAIRE

    Hobai, Ion A.; Aziz, Kanwal; Buys, Emmanuel S.; Brouckaert, Peter; Siwik, Deborah A.; Colucci., Wilson S.

    2016-01-01

    In male mice, Sepsis-Induced Cardiomyopathy develops as a result of dysregulation of myocardial calcium (Ca2+) handling, leading to depressed cellular Ca2+ transients (ΔCai). ΔCai depression is partially due to inhibition of sarcoplasmic reticulum Ca2+ ATP-ase (SERCA) via oxidative modifications, which are partially opposed by cGMP generated by the enzyme soluble guanylyl cyclase (sGC). Whether similar mechanisms underlie Sepsis-Induced Cardiomyopathy in female mice is unknown.

  15. Presynaptic inhibition of synaptic transmission in the rat hippocampus by activation of muscarinic receptors: involvement of presynaptic calcium influx

    OpenAIRE

    Qian, Jing; Saggau, Peter

    1997-01-01

    Modulation of presynaptic voltage-dependent calcium channels (VDCCs) by muscarinic receptors at the CA3–CA1 synapse of rat hippocampal slices was investigated by using the calcium indicator fura-2. Stimulation-evoked presynaptic calcium transients ([Capre]t) and field excitatory postsynaptic potentials (fe.p.s.ps) were simultaneously recorded. The relationship between presynaptic calcium influx and synaptic transmission was studied.Activation of muscarinic receptors inhibited [Capre]t, thereb...

  16. Distribution of voltage-dependent and intracellular Ca2+ channels in submucosal neurons from rat distal colon.

    Science.gov (United States)

    Rehn, Matthias; Bader, Sandra; Bell, Anna; Diener, Martin

    2013-09-01

    We recently observed a bradykinin-induced increase in the cytosolic Ca2+ concentration in submucosal neurons of rat colon, an increase inhibited by blockers of voltage-dependent Ca2+ (Ca(v)) channels. As the types of Ca(v) channels used by this part of the enteric nervous system are unknown, the expression of various Ca(v) subunits has been investigated in whole-mount submucosal preparations by immunohistochemistry. Submucosal neurons, identified by a neuronal marker (microtubule-associated protein 2), are immunoreactive for Ca(v)1.2, Ca(v)1.3 and Ca(v)2.2, expression being confirmed by reverse transcription plus the polymerase chain reaction. These data agree with previous observations that the inhibition of L- and N-type Ca2+ currents strongly inhibits the response to bradykinin. However, whole-cell patch-clamp experiments have revealed that bradykinin does not enhance Ca2+ inward currents under voltage-clamp conditions. Consequently, bradykinin does not directly interact with Ca(v) channels. Instead, the kinin-induced Ca2+ influx is caused indirectly by the membrane depolarization evoked by this peptide. As intracellular Ca2+ channels on Ca(2+)-storing organelles can also contribute to Ca2+ signaling, their expression has been investigated by imaging experiments and immunohistochemistry. Inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) have been functionally demonstrated in submucosal neurons loaded with the Ca(2+)-sensitive fluorescent dye, fura-2. Histamine, a typical agonist coupled to the phospholipase C pathway, induces an increase in the fura-2 signal ratio, which is suppressed by 2-aminophenylborate, a blocker of IP3 receptors. The expression of IP3R1 has been confirmed by immunohistochemistry. In contrast, ryanodine, tested over a wide concentration range, evokes no increase in the cytosolic Ca2+ concentration nor is there immunohistochemical evidence for the expression of ryanodine receptors in these neurons. Thus, rat submucosal neurons are equipped

  17. The inhibitor of connexin Cx36 channels, mefloquine, inhibits voltage-dependent Ca2+channels and insulin secretion.

    Science.gov (United States)

    Seemann, Nele; Welling, Andrea; Rustenbeck, Ingo

    2017-12-05

    The antimalarial agent, mefloquine, inhibits the function of connexin Cx36 gap junctions and hemichannels and has thus become a tool to investigate their physiological relevance in pancreatic islets. In view of earlier reports on a K ATP channel-block by mefloquine, the specificity of mefloquine as a pharmacological tool was investigated. Mouse pancreatic islets and single beta cells were used to measure membrane potential, whole cell currents, Ca 2+ channel activity, cytosolic Ca 2+ concentration ([Ca 2+ ] i ) and insulin secretion. Mefloquine was tested in the concentration range of 5-50 μM 25 μM mefloquine was as effective as 500 μM tolbutamide to depolarize the plasma membrane of beta cells, but did not induce action potentials. Rather, it abolished tolbutamide-induced action potentials and the associated increase of [Ca 2+ ] i . In the range of 5-50 μM mefloquine inhibited voltage-dependent Ca 2+ currents in primary beta cells as effectively as 1 μM nisoldipine, a specific blocker of L-type Ca 2+ channels. The Ca 2+ channel opening effect of Bay K8644 was completely antagonized by mefloquine. Likewise, the increase of [Ca 2+ ] i and of insulin secretion stimulated by 40 mM KCl, but not that by 30 mM glucose was antagonized by 50 μM mefloquine. Neither at 5 μM nor at 50 μM did mefloquin stimulate insulin secretion at basal glucose. In conclusion, mefloquine blocks K ATP channels and L-type Ca 2+ channels in pancreatic beta cells in the range from 5 to 50 μM. Thus it inhibits depolarization-induced insulin secretion, but in the presence of a stimulatory glucose concentration additional effects of mefloquine, possibly on intracellular Ca 2+ mobilization, and the metabolic amplification by glucose permit a sustained rate of secretion. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Action of perchlorate on the voltage dependent inactivation of excitation-contraction coupling in frog skeletal muscle fibres.

    Science.gov (United States)

    Píriz, Nazira; Pizarro, Gonzalo

    2007-01-01

    Perchlorate is an agonist of excitation-contraction coupling (ECC) in skeletal muscle displacing charge movement and release activation towards more negative voltages. Contradictory effects of this compound on the voltage dependent inactivation (VDI) of ECC ranging from no effect to a negative shift have been previously reported. In this study we report the effect of the extracellular application of 8 mM perchlorate to cut frog fibres on: (1) the charge movement that activates release (Q(1)), (2) the charge movement measured in fibres inactivated by depolarization (Q(2)) and (3) on the steady state VDI of Q(1) and Ca(2+) release. Our findings were: (1) The central voltage of Q(1) was negatively displaced by perchlorate from -29.0 +/- 1.6 to -38.4 +/- 1.7 mV (n = 4). The maximum Q(1) was not significantly affected while the slope of the Q(1) vs. V was increased by perchlorate. (2) The central voltage of Q(2) was shifted from -91.6 +/- 1.4 to -102.3 +/- 1.5 mV (n = 4). (3) The central voltage of the steady state inactivation curve of Q(1) went from -39.3 +/- 1.8 to -48.6 +/- 1.2 mV (mean +/- SEM, n = 6). Perchlorate had a paradoxical effect on Ca(2+) release, while potentiated the release flux in fibres held at -90 mV (peak release flux increased from 3.9 +/- 1.1 to 6.8 +/- 1.9 microM/ms, n = 5) it had an inhibitory effect when applied to fibres at a depolarized holding potential (peak release flux decreased from 3.9 +/- 0.9 to 2.0 +/- 0.5 microM/ms, n = 9). The above findings suggest that the effect on the steady state inactivation is a direct consequence of the negative shift in Q(1) activation. The negative shift in the steady state inactivation of Q(1) correlated well with the effect on Ca(2+) release.

  19. Bone morphogenetic protein 4 inhibits insulin secretion from rodent beta cells through regulation of calbindin1 expression and reduced voltage-dependent calcium currents

    DEFF Research Database (Denmark)

    Christensen, Gitte L.; Jacobsen, Maria L. B.; Wendt, Anna

    2015-01-01

    . BMP4-mediated gene expression changes were investigated by microarray profiling, quantitative PCR and western blotting. RESULTS: Prolonged exposure to BMP4 reduced GSIS from rodent pancreatic islets. This inhibition was associated with decreased exocytosis due to a reduced Ca2+ current through voltage...... cells reduced GSIS, and the effect of BMP4 on GSIS was lost in islets from calbindin1 (Calb1) knockout mice. CONCLUSIONS/INTERPRETATION: We found BMP4 treatment to markedly inhibit GSIS from rodent pancreatic islets in a calbindin1-dependent manner. Calbindin1 is suggested to mediate the effect of BMP4...

  20. Heparin/heparan sulfates bind to and modulate neuronal L-type (Cav1.2) voltage-dependent Ca2+ channels

    DEFF Research Database (Denmark)

    Garau, Gianpiero; Magotti, Paola; Heine, Martin

    2015-01-01

    Our previous studies revealed that L-type voltage-dependent Ca2+ channels (Cav1.2 L-VDCCs) are modulated by the neural extracellular matrix backbone, polyanionic glycan hyaluronic acid. Here we used isothermal titration calorimetry and screened a set of peptides derived from the extracellular...... domains of Cav1.2α1 to identify putative binding sites between the channel and hyaluronic acid or another class of polyanionic glycans, such as heparin/heparan sulfates. None of the tested peptides showed detectable interaction with hyaluronic acid, but two peptides derived from the first pore...

  1. Blood flow patterns underlie developmental heart defects.

    Science.gov (United States)

    Midgett, Madeline; Thornburg, Kent; Rugonyi, Sandra

    2017-03-01

    Although cardiac malformations at birth are typically associated with genetic anomalies, blood flow dynamics also play a crucial role in heart formation. However, the relationship between blood flow patterns in the early embryo and later cardiovascular malformation has not been determined. We used the chicken embryo model to quantify the extent to which anomalous blood flow patterns predict cardiac defects that resemble those in humans and found that restricting either the inflow to the heart or the outflow led to reproducible abnormalities with a dose-response type relationship between blood flow stimuli and the expression of cardiac phenotypes. Constricting the outflow tract by 10-35% led predominantly to ventricular septal defects, whereas constricting by 35-60% most often led to double outlet right ventricle. Ligation of the vitelline vein caused mostly pharyngeal arch artery malformations. We show that both cardiac inflow reduction and graded outflow constriction strongly influence the development of specific and persistent abnormal cardiac structure and function. Moreover, the hemodynamic-associated cardiac defects recapitulate those caused by genetic disorders. Thus our data demonstrate the importance of investigating embryonic blood flow conditions to understand the root causes of congenital heart disease as a prerequisite to future prevention and treatment. NEW & NOTEWORTHY Congenital heart defects result from genetic anomalies, teratogen exposure, and altered blood flow during embryonic development. We show here a novel "dose-response" type relationship between the level of blood flow alteration and manifestation of specific cardiac phenotypes. We speculate that abnormal blood flow may frequently underlie congenital heart defects. Copyright © 2017 the American Physiological Society.

  2. Concentration-jump analysis of voltage-dependent conductances activated by glutamate and kainate in neurons of the avian cochlear nucleus.

    Science.gov (United States)

    Raman, I M; Trussell, L O

    1995-01-01

    We have examined the mechanisms underlying the voltage sensitivity of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors in voltage-clamped outside-out patches and whole cells taken from the nucleus magnocellularis of the chick. Responses to either glutamate or kainate had outwardly rectifying current-voltage relations. The rate and extent of desensitization during prolonged exposure to agonist, and the rate of deactivation after brief exposure to agonist, decreased at positive potentials, suggesting that a kinetic transition was sensitive to membrane potential. Voltage dependence of the peak conductance and of the deactivation kinetics persisted when desensitization was reduced with aniracetam or blocked with cyclothiazide. Furthermore, the rate of recovery from desensitization to glutamate was not voltage dependent. Upon reduction of extracellular divalent cation concentration, kainate-evoked currents increased but preserved rectifying current-voltage relations. Rectification was strongest at lower kainate concentrations. Surprisingly, nonstationary variance analysis of desensitizing responses to glutamate or of the current deactivation after kainate removal revealed an increase in the mean single-channel conductance with more positive membrane potentials. These data indicate that the rectification of the peak response to a high agonist concentration reflects an increase in channel conductance, whereas rectification of steady-state current is dominated by voltage-sensitive channel kinetics. Images FIGURE 2 FIGURE 3 PMID:8580330

  3. Physics-Based Compact Model for CIGS and CdTe Solar Cells: From Voltage-Dependent Carrier Collection to Light-Enhanced Reverse Breakdown: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xingshu; Alam, Muhammad Ashraful; Raguse, John; Garris, Rebekah; Deline, Chris; Silverman, Timothy

    2015-10-15

    In this paper, we develop a physics-based compact model for copper indium gallium diselenide (CIGS) and cadmium telluride (CdTe) heterojunction solar cells that attributes the failure of superposition to voltage-dependent carrier collection in the absorber layer, and interprets light-enhanced reverse breakdown as a consequence of tunneling-assisted Poole-Frenkel conduction. The temperature dependence of the model is validated against both simulation and experimental data for the entire range of bias conditions. The model can be used to characterize device parameters, optimize new designs, and most importantly, predict performance and reliability of solar panels including the effects of self-heating and reverse breakdown due to partial-shading degradation.

  4. Voltage-dependent conformational changes in human Ca2+- and voltage-activated K+ channel, revealed by voltage-clamp fluorometry

    Science.gov (United States)

    Savalli, Nicoletta; Kondratiev, Andrei; Toro, Ligia; Olcese, Riccardo

    2006-01-01

    Large conductance voltage- and Ca2+-activated K+ (BKCa) channels regulate important physiological processes such as neurotransmitter release and vascular tone. BKCa channels possess a voltage sensor mainly represented by the S4 transmembrane domain. Changes in membrane potential displace the voltage sensor, producing a conformational change that leads to channel opening. By site-directed fluorescent labeling of residues in the S3–S4 region and by using voltage clamp fluorometry, we have resolved the conformational changes the channel undergoes during activation. The voltage dependence of these conformational changes (detected as changes in fluorescence emission, fluorescence vs. voltage curves) always preceded the channel activation curves, as expected for protein rearrangements associated to the movement of the voltage sensor. Extremely slow conformational changes were revealed by fluorescent labeling of position 202, elicited by a mutual interaction of the fluorophore with the adjacent tryptophan 203. PMID:16895996

  5. Voltage-dependent conformational changes in human Ca(2+)- and voltage-activated K(+) channel, revealed by voltage-clamp fluorometry.

    Science.gov (United States)

    Savalli, Nicoletta; Kondratiev, Andrei; Toro, Ligia; Olcese, Riccardo

    2006-08-15

    Large conductance voltage- and Ca(2+)-activated K(+) (BK(Ca)) channels regulate important physiological processes such as neurotransmitter release and vascular tone. BK(Ca) channels possess a voltage sensor mainly represented by the S4 transmembrane domain. Changes in membrane potential displace the voltage sensor, producing a conformational change that leads to channel opening. By site-directed fluorescent labeling of residues in the S3-S4 region and by using voltage clamp fluorometry, we have resolved the conformational changes the channel undergoes during activation. The voltage dependence of these conformational changes (detected as changes in fluorescence emission, fluorescence vs. voltage curves) always preceded the channel activation curves, as expected for protein rearrangements associated to the movement of the voltage sensor. Extremely slow conformational changes were revealed by fluorescent labeling of position 202, elicited by a mutual interaction of the fluorophore with the adjacent tryptophan 203.

  6. Gate voltage dependent characteristics of p-n diodes and bipolar transistors based on multiwall CN(x)/carbon nanotube intramolecular junctions.

    Science.gov (United States)

    Zhang, W J; Zhang, Q F; Chai, Y; Shen, X; Wu, J L

    2007-10-03

    The electrical transport characteristics of multiwall CN(x)/carbon nanotube intramolecular junctions were studied. The junctions could be used as diodes. We found that the rectification resulted from p-n junctions, not from metal-semiconductor junctions. The gate effect was very weak when the diodes were reverse biased. At forward bias, however, some of the p-n diodes could be n-type transistors. Experimental results supported the opinion that the gate voltage dependent property is derived from the Schottky barrier between the CN(x) part and the electrode. Using p-n diodes, a bipolar transistor with nanoscale components was built, whose behavior was very similar to that of a conventional planar bipolar transistor.

  7. Voltage-Dependent Anion Channel 2 of Arabidopsis thaliana (AtVDAC2 Is Involved in ABA-Mediated Early Seedling Development

    Directory of Open Access Journals (Sweden)

    Xufeng Li

    2009-05-01

    Full Text Available The voltage-dependent anion channel (VDAC is the major transport protein in the outer membrane of mitochondria and plays crucial roles in energy metabolism, apoptosis, and metabolites transport. In plants, the expression of VDACs can be affected by different stresses, including drought, salinity and pathogen defense. In this study, we investigated the expression pattern of AtVDAC2 in A. thaliana and found ABA suppressed the accumulation of AtVDAC2 transcripts. Further, phenotype analysis of this VDAC deregulated-expression transgenic Arabidopsis plants indicated that AtVDAC2 anti-sense line showed an ABA-insensitivity phenotype during the early seedling development under ABA treatment. The results suggested that AtVDAC2 might be involved in ABA signaling in A. thaliana.

  8. Voltage-Dependent Rhythmogenic Property of Respiratory Pre-Bötzinger Complex Glutamatergic, Dbx1-Derived, and Somatostatin-Expressing Neuron Populations Revealed by Graded Optogenetic Inhibition.

    Science.gov (United States)

    Koizumi, Hidehiko; Mosher, Bryan; Tariq, Mohammad F; Zhang, Ruli; Koshiya, Naohiro; Smith, Jeffrey C

    2016-01-01

    The rhythm of breathing in mammals, originating within the brainstem pre-Bötzinger complex (pre-BötC), is presumed to be generated by glutamatergic neurons, but this has not been directly demonstrated. Additionally, developmental expression of the transcription factor Dbx1 or expression of the neuropeptide somatostatin (Sst), has been proposed as a marker for the rhythmogenic pre-BötC glutamatergic neurons, but it is unknown whether these other two phenotypically defined neuronal populations are functionally equivalent to glutamatergic neurons with regard to rhythm generation. To address these problems, we comparatively investigated, by optogenetic approaches, the roles of pre-BötC glutamatergic, Dbx1-derived, and Sst-expressing neurons in respiratory rhythm generation in neonatal transgenic mouse medullary slices in vitro and also more intact adult perfused brainstem-spinal cord preparations in situ. We established three different triple-transgenic mouse lines with Cre-driven Archaerhodopsin-3 (Arch) expression selectively in glutamatergic, Dbx1-derived, or Sst-expressing neurons for targeted photoinhibition. In each line, we identified subpopulations of rhythmically active, Arch-expressing pre-BötC inspiratory neurons by whole-cell recordings in medullary slice preparations in vitro, and established that Arch-mediated hyperpolarization of these inspiratory neurons was laser power dependent with equal efficacy. By site- and population-specific graded photoinhibition, we then demonstrated that inspiratory frequency was reduced by each population with the same neuronal voltage-dependent frequency control mechanism in each state of the respiratory network examined. We infer that enough of the rhythmogenic pre-BötC glutamatergic neurons also have the Dbx1 and Sst expression phenotypes, and thus all three phenotypes share the same voltage-dependent frequency control property.

  9. Voltage-Dependent Rhythmogenic Property of Respiratory Pre-Bötzinger Complex Glutamatergic, Dbx1-Derived, and Somatostatin-Expressing Neuron Populations Revealed by Graded Optogenetic Inhibition123

    Science.gov (United States)

    Koizumi, Hidehiko; Mosher, Bryan; Tariq, Mohammad F.; Zhang, Ruli

    2016-01-01

    Abstract The rhythm of breathing in mammals, originating within the brainstem pre-Bötzinger complex (pre-BötC), is presumed to be generated by glutamatergic neurons, but this has not been directly demonstrated. Additionally, developmental expression of the transcription factor Dbx1 or expression of the neuropeptide somatostatin (Sst), has been proposed as a marker for the rhythmogenic pre-BötC glutamatergic neurons, but it is unknown whether these other two phenotypically defined neuronal populations are functionally equivalent to glutamatergic neurons with regard to rhythm generation. To address these problems, we comparatively investigated, by optogenetic approaches, the roles of pre-BötC glutamatergic, Dbx1-derived, and Sst-expressing neurons in respiratory rhythm generation in neonatal transgenic mouse medullary slices in vitro and also more intact adult perfused brainstem-spinal cord preparations in situ. We established three different triple-transgenic mouse lines with Cre-driven Archaerhodopsin-3 (Arch) expression selectively in glutamatergic, Dbx1-derived, or Sst-expressing neurons for targeted photoinhibition. In each line, we identified subpopulations of rhythmically active, Arch-expressing pre-BötC inspiratory neurons by whole-cell recordings in medullary slice preparations in vitro, and established that Arch-mediated hyperpolarization of these inspiratory neurons was laser power dependent with equal efficacy. By site- and population-specific graded photoinhibition, we then demonstrated that inspiratory frequency was reduced by each population with the same neuronal voltage-dependent frequency control mechanism in each state of the respiratory network examined. We infer that enough of the rhythmogenic pre-BötC glutamatergic neurons also have the Dbx1 and Sst expression phenotypes, and thus all three phenotypes share the same voltage-dependent frequency control property. PMID:27275007

  10. The effect of calcium on auxin depletion-induced tomato ...

    African Journals Online (AJOL)

    Indole-3-acetic acid (IAA) and calcium are the most important factors that instigate plant organ abscission. This study aimed to elucidate the mechanisms that underlie the effects of IAA and calcium on delayed abscission in tomato. The results showed a clear trend towards reduced abscission rates with increased ...

  11. Altered gating and local anesthetic block mediated by residues in the I-S6 and II-S6 transmembrane segments of voltage-dependent Na+ channels.

    Science.gov (United States)

    Kondratiev, Andrei; Tomaselli, Gordon F

    2003-09-01

    The cytoplasmic side of the voltage-dependent Na+ channel pore is putatively formed by the S6 segments of domains I to IV. The role of amino acid residues of I-S6 and II-S6 in channel gating and local anesthetic (LA) block was investigated using the cysteine scanning mutagenesis of the rat skeletal muscle Na+ channel (Nav1.4). G428C uniquely reduced sensitivity to rested state or first-pulse block by lidocaine without alterations in the voltage dependence or kinetics of gating that would otherwise account for the increase in the IC50 for block. Mutations in I-S6 (N434C and I436C) and in II-S6 (L785C and V787C) increased sensitivity to first-pulse block by lidocaine. Enhanced inactivation accounted for the increased sensitivity of N434C to lidocaine and hastening of inactivation of I436C in the absence of drug could account for higher affinity first-pulse block. Mutations in I-S6 (I424C, I425C, and F430C) and in II-S6 (I782C and V786C) reduced the use-dependent lidocaine block. The reduction in use-dependent block of F430C was consistent with alterations in inactivation gating; the other mutants did not exhibit gating changes that could explain the reduced sensitivity to lidocaine. Therefore, several amino acids (I424, I425, G428, I782, and V786), in addition to those previously identified (Yarov-Yarovoy et al., 2002), alter the sensitivity of Nav1.4 to lidocaine, independent of mutation-induced changes in gating. The magnitude of the change in the IC50 values, the isoform, and LA dependence of the changes in affinity suggest that the determinants of binding in I-S6 and II-S6 are subsidiary to those in IV-S6.

  12. Dual action of a dinoflagellate-derived precursor of Pacific ciguatoxins (P-CTX-4B) on voltage-dependent K(+) and Na(+) channels of single myelinated axons.

    Science.gov (United States)

    Schlumberger, Sébastien; Mattei, César; Molgó, Jordi; Benoit, Evelyne

    2010-10-01

    The effects of Pacific ciguatoxin-4B (P-CTX-4B, also named gambiertoxin), extracted from toxic Gambierdiscus dinoflagellates, were assessed on nodal K(+) and Na(+) currents of frog myelinated axons, using a conventional voltage-clamp technique. P-CTX-4B decreased, within a few minutes, both K(+) and Na(+) currents in a dose-dependent manner, without inducing any marked change in current kinetics. The toxin was more effective in blocking K(+) than Na(+) channels. P-CTX-4B shifted the voltage-dependence of Na(+) conductance by about 14 mV towards more negative membrane potentials. This effect was reversed by increasing Ca(2+) in the external solution. A negative shift of about 16 mV in the steady-state Na(+) inactivation-voltage curve was also observed in the presence of the toxin. Unmodified and P-CTX-4B-modified Na(+) currents were similarly affected by the local anaesthetic lidocaine. The decrease of the two currents by lidocaine was dependent on both the concentration and the membrane potential during pre-pulses. In conclusion, P-CTX-4B appears about four times more effective than P-CTX-1B to affect K(+) channels, whereas it is about 50 times less efficient to affect Na(+) channels of axonal membranes. These actions may be related to subtle differences between the two chemical structures of molecules. Copyright 2009 Elsevier Ltd. All rights reserved.

  13. Bias-voltage dependent ultraviolet photodetectors prepared by GaO{sub x} + ZnO mixture phase nanocrystalline thin films

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Rongxin, E-mail: rxwang2008@sinano.ac.cn [Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123 (China); Yang, Lechen [Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123 (China); Xu, Shijie [Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123 (China); Department of Physics and HKU-CAS Joint Laboratory on New Materials, The University of Hong Kong, Pokfulam Road, Hong Kong (China); Zhang, Xiaodong; Dong, Xue; Zhao, Yingchun; Fu, Kai; Zhang, Baoshun; Yang, Hui [Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123 (China)

    2013-07-25

    Highlights: •GaO{sub x} + ZnO thin films sputtered and annealed exhibit interesting and unique optical properties, especially deep UV photo response. •GaO{sub x} + ZnO thin films can be used to fabricate efficient deep UV photodetectors. •The mixture phase nature of GaO{sub x} + ZnO thin films is revealed to be responsible for the unique characteristics of the photodetectors. •Two bands in UV range can be adjusted by a applied voltage when the PDs were fabricated using the mixture phase nature of GaO{sub x} + ZnO thin films. -- Abstract: Ultraviolet (UV) photodetectors were prepared by using the GaO{sub x} + ZnO mixture phase thin films sputtered on sapphire as the photoresponse layer. The devices show good photoresponse in UV range. More interestingly, the device responsivity in the wavelength less than 280 nm range rapidly increases with increasing the applied voltage and becomes dominant for the bias ⩾3.0 V. X-ray diffraction, absorption and cathodoluminescence measurements firmly reveal the mixture phases in the thin films. Electric field dependent detrapping of photo-excited carriers in nanocrystals in the films shall be responsible for the observed bias-voltage dependent deep UV photoresponse of the devices.

  14. Fluorescence resonance energy transfer on the voltage-dependent sodium channel. Spatial relationship and site coupling between the batrachotoxin and Leiurus quinquestriatus quinquestriatus alpha-scorpion toxin receptors.

    Science.gov (United States)

    Angelides, K J; Brown, G B

    1984-05-25

    A fluorescent N- methylanthraniloyl derivative of the potent depolarizing agent batrachotoxin has been used to probe the structural and conformational properties of the neurotoxin receptor site on the voltage-dependent sodium channel. Batrachotoxin A 20-alpha-N- methylanthranilate (BTX-NMA) retains high affinity for its receptor site on the synaptosomal sodium channel with a Kd between 78 and 91 nM and an average site capacity of 2 pmol/mg of synaptosomal protein in the presence of Leiurus quinquestriatus quinquestriatus alpha-scorpion toxin. The fluorescence emission of BTX-NMA upon binding to synaptosomes indicates a hydrophobic environment. Toxin V from L. quinquestriatus, an allosteric activator, effects a 20-nm red shift in the spectrum of bound BTX-NMA and a 4-fold enhancement in the fluorescence quantum yield disclosing a conformational change into a hydrophilic environment. Fluorescence resonance energy transfer measurements show that the distance separating the receptor sites is 37 +/- 10 A. Thus, the binding of alpha-scorpion toxin must involve conformational changes that extend over large distances from the batrachotoxin-binding locus. This information together with the distance measurements between the tetrodotoxin and alpha-scorpion toxin receptors and the conformational transition associated with this distance upon batrachotoxin addition indicate a conformationally flexible channel with coupling of sites through the polyatomic framework of individual subunits or through extensive alterations in subunit/subunit interactions.

  15. A Gating Model for the Archeal Voltage-Dependent K+ Channel KvAP in DPhPC and POPE:POPG decane lipid bilayers

    Science.gov (United States)

    Schmidt, Daniel; Cross, Sam R.; MacKinnon, Roderick

    2009-01-01

    Voltage-dependent K+ (Kv) channels form the basis of the excitability of nerves and muscles. KvAP is a well-characterized archeal Kv channel that has been widely used to investigate many aspects of Kv channel biochemistry, biophysics and structure. In this study a minimal kinetic gating model for KvAP function in two different phospholipid decane bilayers is developed. In most aspects KvAP gating is similar to the well-studied eukaryotic Shaker Kv channel: conformational changes occur within four voltage sensors followed by pore opening. Unlike Shaker, KvAP possesses an inactivated state that is accessible from the pre-open state of the channel. Changing the lipid composition of the membrane influences multiple gating transitions in the model, but most dramatically the rate of recovery from inactivation. Inhibition by the voltage sensor toxin VSTx1 is most easily explained if VSTx1 binds only to the depolarized conformation of the voltage sensor. By delaying the voltage sensor’s return to the hyperpolarized conformation VSTx1 favors the inactivated state of KvAP. PMID:19481093

  16. A gating model for the archeal voltage-dependent K(+) channel KvAP in DPhPC and POPE:POPG decane lipid bilayers.

    Science.gov (United States)

    Schmidt, Daniel; Cross, Samuel R; MacKinnon, Roderick

    2009-07-31

    Voltage-dependent K(+) (Kv) channels form the basis of the excitability of nerves and muscles. KvAP is a well-characterized archeal Kv channel that has been widely used to investigate many aspects of Kv channel biochemistry, biophysics, and structure. In this study, a minimal kinetic gating model for KvAP function in two different phospholipid decane bilayers is developed. In most aspects, KvAP gating is similar to the well-studied eukaryotic Shaker Kv channel: conformational changes occur within four voltage sensors, followed by pore opening. Unlike the Shaker Kv channel, KvAP possesses an inactivated state that is accessible from the pre-open state of the channel. Changing the lipid composition of the membrane influences multiple gating transitions in the model, but, most dramatically, the rate of recovery from inactivation. Inhibition by the voltage sensor toxin VSTx1 is most easily explained if VSTx1 binds only to the depolarized conformation of the voltage sensor. By delaying the voltage sensor's return to the hyperpolarized conformation, VSTx1 favors the inactivated state of KvAP.

  17. Mitochondria-associated Endoplasmic Reticulum Membrane (MAM) Regulates Steroidogenic Activity via Steroidogenic Acute Regulatory Protein (StAR)-Voltage-dependent Anion Channel 2 (VDAC2) Interaction*

    Science.gov (United States)

    Prasad, Manoj; Kaur, Jasmeet; Pawlak, Kevin J.; Bose, Mahuya; Whittal, Randy M.; Bose, Himangshu S.

    2015-01-01

    Steroid hormones are essential for carbohydrate metabolism, stress management, and reproduction and are synthesized from cholesterol in mitochondria of adrenal glands and gonads/ovaries. In acute stress or hormonal stimulation, steroidogenic acute regulatory protein (StAR) transports substrate cholesterol into the mitochondria for steroidogenesis by an unknown mechanism. Here, we report for the first time that StAR interacts with voltage-dependent anion channel 2 (VDAC2) at the mitochondria-associated endoplasmic reticulum membrane (MAM) prior to its translocation to the mitochondrial matrix. In the MAM, StAR interacts with mitochondrial proteins Tom22 and VDAC2. However, Tom22 knockdown by siRNA had no effect on pregnenolone synthesis. In the absence of VDAC2, StAR was expressed but not processed into the mitochondria as a mature 30-kDa protein. VDAC2 interacted with StAR via its C-terminal 20 amino acids and N-terminal amino acids 221–229, regulating the mitochondrial processing of StAR into the mature protein. In the absence of VDAC2, StAR could not enter the mitochondria or interact with MAM-associated proteins, and therefore steroidogenesis was inhibited. Furthermore, the N terminus was not essential for StAR activity, and the N-terminal deletion mutant continued to interact with VDAC2. The endoplasmic reticulum-targeting prolactin signal sequence did not affect StAR association with the MAM and thus its mitochondrial targeting. Therefore, VDAC2 controls StAR processing and activity, and MAM is thus a central location for initiating mitochondrial steroidogenesis. PMID:25505173

  18. Mitochondria-associated endoplasmic reticulum membrane (MAM) regulates steroidogenic activity via steroidogenic acute regulatory protein (StAR)-voltage-dependent anion channel 2 (VDAC2) interaction.

    Science.gov (United States)

    Prasad, Manoj; Kaur, Jasmeet; Pawlak, Kevin J; Bose, Mahuya; Whittal, Randy M; Bose, Himangshu S

    2015-01-30

    Steroid hormones are essential for carbohydrate metabolism, stress management, and reproduction and are synthesized from cholesterol in mitochondria of adrenal glands and gonads/ovaries. In acute stress or hormonal stimulation, steroidogenic acute regulatory protein (StAR) transports substrate cholesterol into the mitochondria for steroidogenesis by an unknown mechanism. Here, we report for the first time that StAR interacts with voltage-dependent anion channel 2 (VDAC2) at the mitochondria-associated endoplasmic reticulum membrane (MAM) prior to its translocation to the mitochondrial matrix. In the MAM, StAR interacts with mitochondrial proteins Tom22 and VDAC2. However, Tom22 knockdown by siRNA had no effect on pregnenolone synthesis. In the absence of VDAC2, StAR was expressed but not processed into the mitochondria as a mature 30-kDa protein. VDAC2 interacted with StAR via its C-terminal 20 amino acids and N-terminal amino acids 221-229, regulating the mitochondrial processing of StAR into the mature protein. In the absence of VDAC2, StAR could not enter the mitochondria or interact with MAM-associated proteins, and therefore steroidogenesis was inhibited. Furthermore, the N terminus was not essential for StAR activity, and the N-terminal deletion mutant continued to interact with VDAC2. The endoplasmic reticulum-targeting prolactin signal sequence did not affect StAR association with the MAM and thus its mitochondrial targeting. Therefore, VDAC2 controls StAR processing and activity, and MAM is thus a central location for initiating mitochondrial steroidogenesis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Leftward shift in the voltage-dependence for Ca2+ currents activation induced by a new toxin from Phoneutria reidyi (Aranae, Ctenidae) venom.

    Science.gov (United States)

    Vieira, L B; Pimenta, A M C; Richardson, M; Bemquerer, M P; Reis, H J; Cruz, J S; Gomez, M V; Santoro, M M; Ferreira-de-Oliveira, R; Figueiredo, S G; Snutch, T P; Cordeiro, M N

    2007-02-01

    Various neurotoxins have been described from the venom of the Brazilian spider Phoneutria nigriventer, but little is known about the venoms of the other species of this genus. In the present work, we describe the purification and some structural and pharmacological features of a new toxin (PRTx3-7) from Phoneutria reidyi that causes flaccid paralysis in mice. The observed molecular mass (4627.26 Da) was in accordance with the calculated mass for the amidated form of the amino acid sequence (4627.08 Da). The presence of an alpha-amidated C-terminus was confirmed by MS/MS analysis of the C-terminal peptide, isolated after enzymatic digestion of the native protein with Glu-C endoproteinase. The purified protein was injected (intracerebro-ventricular) into mice at dose levels of 5 microg/mouse causing immediate agitation and clockwise gyration, followed by the gradual development of general flaccid paralysis. PRTx3-7 at 1 microM inhibited by 20% the KCl-induced increase on [Ca2+]i in rat brain synaptosomes. The HEK cells permanently expressing L, N, P/Q and R HVA Ca2+ channels were also used to better characterize the pharmacological features of PRTx3-7. To our surprise, PRTx3-7 shifted the voltage-dependence for activation towards hyperpolarized membrane potentials for L (-4 mV), P/Q (-8 mV) and R (-5 mV) type Ca2+ currents. In addition, the new toxin also affected the steady state of inactivation of L-, N- and P/Q-type Ca2+ currents.

  20. Stimulation of Na+-alanine cotransport activates a voltage-dependent conductance in single proximal tubule cells isolated from frog kidney

    Science.gov (United States)

    Robson, L; Hunter, M

    1999-01-01

    The swelling induced by Na+-alanine cotransport in proximal tubule cells of the frog kidney is followed by regulatory volume decrease (RVD). This RVD is inhibited by gadolinium (Gd3+), an inhibitor of stretch-activated channels, but is independent of extracellular Ca2+. In this study, the whole cell patch clamp technique was utilized to examine the effect of Na+-alanine cotransport on two previously identified volume- and Gd3+-sensitive conductances. One conductance is voltage dependent and anion selective (GVD) whilst the other is voltage independent and cation selective (GVI). Addition of 5 mM L-alanine to the bathing solution increased the whole cell conductance and gave a positive (depolarizing) shift in the reversal potential (Vrev, equivalent to the membrane potential in current-clamped cells) consistent with activation of Na+-alanine cotransport. Vrev shifted from -36 ± 4·9 to +12·9 ± 4·2 mV (n= 15). In the presence of alanine, the total whole cell conductance had several components including the cotransporter conductance and GVD and GVI. These conductances were separated using Gd3+, which inhibits both GVD and GVI, and the time dependency of GVD. Of these two volume-sensitive conductances, L-alanine elicited a specific increase in GVD, whereas GVI was unaffected. The L-alanine-induced activation of GVD was significantly reduced when cells were incubated in a hypertonic bathing solution. In summary, in single proximal tubule cells isolated from frog kidney, on stimulation of Na+-alanine cotransport GVD is activated, while GVI is unaffected. Taken with other evidence, this suggests that GVD is activated by cell swelling, consequent upon alanine entry, and may play a role as an anion efflux pathway during alanine-induced volume regulation. PMID:10226159

  1. Frequency and voltage dependence dielectric properties, ac electrical conductivity and electric modulus profiles in Al/Co{sub 3}O{sub 4}-PVA/p-Si structures

    Energy Technology Data Exchange (ETDEWEB)

    Bilkan, Çiğdem, E-mail: cigdembilkan@gmail.com [Department of Physics, Faculty of Sciences, The University of Çankırı Karatekin, 18100 Çankırı (Turkey); Azizian-Kalandaragh, Yashar [Department of Physics, Faculty of Science, The University of Mohaghegh Ardabili, Ardabil (Iran, Islamic Republic of); Altındal, Şemsettin [Department of Physics, Faculty of Sciences, The University of Gazi, 06500 Ankara (Turkey); Shokrani-Havigh, Roya [Department of Physics, Faculty of Science, The University of Mohaghegh Ardabili, Ardabil (Iran, Islamic Republic of)

    2016-11-01

    In this research a simple microwave-assisted method have been used for preparation of cobalt oxide nanostructures. The as-prepared sample has been investigated by UV–vis spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM). On the other hand, frequency and voltage dependence of both the real and imaginary parts of dielectric constants (ε′, ε″) and electric modulus (M′ and M″), loss tangent (tanδ), and ac electrical conductivity (σ{sub ac}) values of Al/Co{sub 3}O{sub 4}-PVA/p-Si structures were obtained in the wide range of frequency and voltage using capacitance (C) and conductance (G/ω) data at room temperature. The values of ε′, ε″ and tanδ were found to decrease with increasing frequency almost for each applied bias voltage, but the changes in these parameters become more effective in the depletion region at low frequencies due to the charges at surface states and their relaxation time and polarization effect. While the value of σ is almost constant at low frequency, increases almost as exponentially at high frequency which are corresponding to σ{sub dc} and σ{sub ac}, respectively. The M′ and M″ have low values at low frequencies region and then an increase with frequency due to short-range mobility of charge carriers. While the value of M′ increase with increasing frequency, the value of M″ shows two peak and the peaks positions shifts to higher frequency with increasing applied voltage due to the decrease of the polarization and N{sub ss} effects with increasing frequency.

  2. The junctional SR protein JP-45 affects the functional expression of the voltage-dependent Ca2+ channel Cav1.1.

    Science.gov (United States)

    Anderson, Ayuk A; Altafaj, Xavier; Zheng, Zhenlin; Wang, Zhong-Min; Delbono, Osvaldo; Ronjat, Michel; Treves, Susan; Zorzato, Francesco

    2006-05-15

    JP-45, an integral protein of the junctional face membrane of the skeletal muscle sarcoplasmic reticulum (SR), colocalizes with its Ca2+ -release channel (the ryanodine receptor), and interacts with calsequestrin and the skeletal-muscle dihydropyridine receptor Cav1. We have identified the domains of JP-45 and the Cav1.1 involved in this interaction, and investigated the functional effect of JP-45. The cytoplasmic domain of JP-45, comprising residues 1-80, interacts with Cav1.1. JP-45 interacts with two distinct and functionally relevant domains of Cav1.1, the I-II loop and the C-terminal region. Interaction between JP-45 and the I-II loop occurs through the alpha-interacting domain in the I-II loop. beta1a, a Cav1 subunit, also interacts with the cytosolic domain of JP-45, and its presence drastically reduces the interaction between JP-45 and the I-II loop. The functional effect of JP-45 on Cav1.1 activity was assessed by investigating charge movement in differentiated C2C12 myotubes after overexpression or depletion of JP-45. Overexpression of JP-45 decreased peak charge-movement and shifted VQ1/2 to a more negative potential (-10 mV). JP-45 depletion decreased both the content of Cav1.1 and peak charge-movements. Our data demonstrate that JP-45 is an important protein for functional expression of voltage-dependent Ca2+ channels.

  3. A conserved threonine in the S1-S2 loop of KV7.2 and K V7.3 channels regulates voltage-dependent activation.

    Science.gov (United States)

    Füll, Yvonne; Seebohm, Guiscard; Lerche, Holger; Maljevic, Snezana

    2013-06-01

    The voltage-gated potassium channels KV7.2 and KV7.3 (KCNQ2/3 genes) play an important role in regulating neuronal excitability. More than 50 KCNQ2/3 mutations have been identified to cause an inherited form of epilepsy in newborns. For two of those (E119G and S122L) found in the S1-S2 region of KV7.2, we previously showed a decreased channel availability mainly at action potential subthreshold voltages caused by a slight depolarizing shift of the activation curve. Interestingly, recent studies revealed that a threonine residue within the S1-S2 loop, highly conserved among different classes of KV channels, is crucial for both their function and surface expression. To investigate the functional role of the homologous threonine residues in KV7.2 (T114) and KV7.3 (T144) channels, we replaced them with alanine and examined the electrophysiological properties using heterologous expression in CHO cells and whole cell patch clamping. Channels comprising mutant subunits yielded decreased potassium currents with slowed activation and accelerated deactivation kinetics. However, the most striking effect was a depolarizing shift in the voltage dependence of activation reaching +30 mV upon co-expression of both mutant subunits. Potential interactions of T114 within the channel were analyzed by creating a 3D homology model of KV7.2 in an open state suggesting that this residue plays a central role in the formation of a stable interface between the S1-S2 and the S5 segment helices. This could be the explanation why substitution of the conserved threonine in KV7.2 and KV7.3 channels destabilizes the open and favors the closed state of these channels.

  4. Direct modulation of the outer mitochondrial membrane channel, voltage-dependent anion channel 1 (VDAC1) by cannabidiol: a novel mechanism for cannabinoid-induced cell death

    OpenAIRE

    Rimmerman, N; Ben-Hail, D; Porat, Z; Juknat, A; Kozela, E; Daniels, M P; Connelly, P S; Leishman, E; Bradshaw, H B; Shoshan-Barmatz, V; Vogel, Z

    2013-01-01

    Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that inhibits cell proliferation and induces cell death of cancer cells and activated immune cells. It is not an agonist of the classical CB1/CB2 cannabinoid receptors and the mechanism by which it functions is unknown. Here, we studied the effects of CBD on various mitochondrial functions in BV-2 microglial cells. Our findings indicate that CBD treatment leads to a biphasic increase in intracellular calcium levels and to changes in mi...

  5. A quantitative and comparative study of the effects of a synthetic ciguatoxin CTX3C on the kinetic properties of voltage-dependent sodium channels

    Science.gov (United States)

    Yamaoka, Kaoru; Inoue, Masayuki; Miyahara, Hidemichi; Miyazaki, Keisuke; Hirama, Masahiro

    2004-01-01

    Ciguatoxins (CTXs) are known to bind to receptor site 5 of the voltage-dependent Na channel, but the toxin's physiological effects are poorly understood. In this study, we investigated the effects of a ciguatoxin congener (CTX3C) on three different Na-channel isoforms, rNav1.2, rNav1.4, and rNav1.5, which were transiently expressed in HEK293 cells. The toxin (1.0 μmol l−1) shifted the activation potential (V1/2 of activation curve) in the negative direction by 4–9 mV and increased the slope factor (k) from 8 mV to between 9 and 12 mV (indicative of decreased steepness of the activation curve), thereby resulting in a hyperpolarizing shift of the threshold potential by 30 mV for all Na channel isoforms. The toxin (1.0 μmol l−1) significantly accelerated the time-to-peak current from 0.62 to 0.52 ms in isoform rNav1.2. Higher doses of the toxin (3–10 μmol l−1) additionally decreased time-to-peak current in rNav1.4 and rNav1.5. A toxin effect on decay of INa at −20 mV was either absent or marginal even at relatively high doses of CTX3C. The toxin (1 μmol l−1) shifted the inactivation potential (V1/2 of inactivation curve) in the negative direction by 15–18 mV in all isoforms. INa maxima of the I–V curve (at −20 mV) were suppressed by application of 1.0 μmol l−1 CTX3C to a similar extent (80–85% of the control) in all the three isoforms. Higher doses of CTX3C up to 10 μmol l−1 further suppressed INa to 61–72% of the control. Recovery from slow inactivation induced by a depolarizing prepulse of intermediate duration (500 ms) was dramatically delayed in the presence of 1.0 μmol l−1 CTX3C, as time constants describing the monoexponential recovery were increased from 38±8 to 588±151 ms (n=5), 53±6 to 338±85 ms (n=4), and 23±3 to 232±117 ms (n=3) in rNav1.2, rNav1.4, and rNav1.5, respectively. CTX3C exerted multimodal effects on sodium channels, with simultaneous stimulatory and inhibitory aspects, probably due to the large

  6. Dissociation of charge movement from calcium release and calcium current in skeletal myotubes by gabapentin.

    Science.gov (United States)

    Alden, Kris J; García, Jesús

    2002-09-01

    The skeletal muscle L-type calcium channel or dihydropyridine receptor (DHPR) plays an integral role in excitation-contraction (E-C) coupling. Its activation initiates three sequential events: charge movement (Q(r)), calcium release, and calcium current (I(Ca,L)). This relationship suggests that changes in Q(r) might affect release and I(Ca,L). Here we studied the effect of gabapentin (GBP) on the three events generated by DHPRs in skeletal myotubes in culture. GBP specifically binds to the alpha(2)/delta(1) subunit of the brain and skeletal muscle DHPR. Myotubes were stimulated with a protocol that included a depolarizing prepulse to inactivate voltage-dependent proteins other than DHPRs. Gabapentin (50 microM) significantly increased Q(r) while decreasing the rate of rise of calcium transients. Gabapentin also reduced the maximum amplitude of the I(Ca,L) (as we previously reported) without modifying the kinetics of activation. Exposure of GBP-treated myotubes to 10 microM nifedipine prevented the increase of Q(r) promoted by this drug, indicating that the extra charge recorded originated from DHPRs. Our data suggest that GBP dissociates the functions of the DHPR from the initial voltage-sensing step and implicates a role for the alpha(2)/delta(1) subunit in E-C coupling.

  7. Calcium Electroporation

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gibot, Laure; Madi, Moinecha

    2015-01-01

    ), and a breast adenocarcinoma (MDA-MB231), as well as on primary normal human dermal fibroblasts (HDF-n). RESULTS: The results showed a clear reduction in spheroid size in all three cancer cell spheroids three days after treatment with respectively calcium electroporation (p...-malignant as well as normal. CONCLUSION: In conclusion, calcium electroporation seems to be more effective in inducing cell death in cancer cell spheroids than in a normal fibroblast spheroid, even though intracellular ATP level is depleted in all spheroid types after treatment. These results may indicate......BACKGROUND: Calcium electroporation describes the use of high voltage electric pulses to introduce supraphysiological calcium concentrations into cells. This promising method is currently in clinical trial as an anti-cancer treatment. One very important issue is the relation between tumor cell kill...

  8. Calcium channel activity of purified human synexin and structure of the human synexin gene

    International Nuclear Information System (INIS)

    Burns, A.L.; Magendzo, K.; Shirvan, A.; Srivastava, M.; Rojas, E.; Alijani, M.R.; Pollard, H.B.

    1989-01-01

    Synexin is a calcium-dependent membrane binding protein that not only fuses membranes but also acts as a voltage-dependent calcium channel. The authors have isolated and sequenced a set of overlapping cDNA clones for human synexin. The derived amino acid sequence of synexin reveals strong homology in the C-terminal domain with a previously identified class of calcium-dependent membrane binding proteins. These include endonexin II, lipocortin I, calpactin I heavy chain (p36), protein II, and calelectrin 67K. The M r 51,000 synexin molecule can be divided into a unique, highly hydrophobic N-terminal domain of 167 amino acids and a conserved C-terminal region of 299 amino acids. The latter domain is composed of alternating hydrophobic and hydrophilic segments. Analysis of the entire structure reveals possible insights into such diverse properties as voltage-sensitive calcium channel activity, ion selectivity, affinity for phospholipids, and membrane fusion

  9. Calcium channel blockers in cardiovascular pharmacotherapy.

    Science.gov (United States)

    Godfraind, Theophile

    2014-11-01

    This paper summarizes the pharmacological properties of calcium channel blockers (CCBs), their established therapeutic uses for cardiovascular disorders and the current improvement of their clinical effects through drug combinations. Their identification resulted from study of small molecules including coronary dilators, which were named calcium antagonists. Further experiments showed that they reduced contraction of arteries by inhibiting calcium entry and by interacting with binding sites identified on voltage-dependent calcium channels. This led to the denomination calcium channel blockers. In short-term studies, by decreasing total peripheral resistance, CCBs lower arterial pressure. By unloading the heart and increasing coronary blood flow, CCBs improve myocardial oxygenation. In long-term treatment, the decrease in blood pressure is more pronounced in hypertensive than in normotensive patients. A controversy on the safety of CCBs ended after a large antihypertensive trial (ALLHAT) sponsored by the National Heart, Lung, and Blood Institute. There are two main types of CCBs: dihydopyridine and non-dihydropyridine; the first type is vascular selective. Dihydropyrines are indicated for hypertension, chronic, stable and vasospastic angina. Non-dihydropyridines have the same indications plus antiarrythmic effects in atrial fibrillation or flutter and paroxysmal supraventricular tachycardia. In addition, CCBs reduced newly formed coronary lesions in atherosclerosis. In order to reach recommended blood pressure goals, there is a recent therapeutic move by combination of CCBs with other antihypertensive agents particularly with inhibitors acting at the level of the renin-angiotensin system. They are also combined with statins. Prevention of dementia has been reported in hypertensive patients treated with nitrendipine, opening a way for further studies on CCBs' beneficial effect in cognitive deterioration associated with aging. © The Author(s) 2014.

  10. Chronic electroconvulsive stimulation but not chronic restraint stress modulates mRNA expression of voltage-dependent potassium channels Kv7.2 and Kv11.1 in the rat piriform cortex

    DEFF Research Database (Denmark)

    Hjæresen, Marie-Louise; Hageman, Ida; Wörtwein, Gitta

    2008-01-01

    The mechanisms by which stress and electroconvulsive therapy exert opposite effects on the course of major depression are not known. Potential candidates might include the voltage-dependent potassium channels. Potassium channels play an important role in maintaining the resting membrane potential...... and controlling neuronal excitability. To explore this hypothesis, we examined the effects of one or several electroconvulsive stimulations and chronic restraint stress (6 h/day for 21 days) on the expression of voltage-dependent potassium channel Kv7.2, Kv11.1, and Kv11.3 mRNA in the rat brain using in situ...... hybridization. Repeated, but not acute, electroconvulsive stimulation increased Kv7.2 and Kv11.1 mRNA levels in the piriform cortex. In contrast, restraint stress had no significant effect on mRNA expression of Kv7.2, Kv11.1, or Kv11.3 in any of the brain regions examined. Thus, it appears that the investigated...

  11. Kv4 channels underlie the subthreshold-operating A-type K+-current in nociceptive dorsal root ganglion neurons

    Directory of Open Access Journals (Sweden)

    Thanawath R Na Phuket

    2009-07-01

    Full Text Available The dorsal root ganglion (DRG contains heterogeneous populations of sensory neurons including primary nociceptive neurons and C-fibers implicated in pain signaling.  Recent studies have demonstrated DRG hyperexcitability associated with downregulation of A-type K+ channels; however, the molecular correlate of the corresponding A-type K+ current (IA has remained hypothetical.  Kv4 channels may underlie the IA in DRG neurons.  We combined electrophysiology, molecular biology (whole-tissue and single-cell RT-PCR and immunohistochemistry to investigate the molecular basis of the IA in acutely dissociated DRG neurons from 7-8 day-old rats.  Whole-cell recordings demonstrate a robust tetraethylammonium-resistant (20 mM and 4-aminopyridine-sensitive (5 mM IA.  Matching Kv4 channel properties, activation and inactivation of this IA occur in the subthreshold range of membrane potentials and the rate of recovery from inactivation is rapid and voltage-dependent.  Among Kv4 transcripts, the DRG expresses significant levels of Kv4.1 and Kv4.3 mRNAs.  Also, single small-medium diameter DRG neurons (~30 mm exhibit correlated frequent expression of mRNAs encoding Kv4.1 and Nav1.8, a known nociceptor marker.  In contrast, the expressions of Kv1.4 and Kv4.2 mRNAs at the whole-tissue and single-cell levels are relatively low and infrequent.  Kv4 protein expression in nociceptive DRG neurons was confirmed by immunohistochemistry, which demonstrates colocalization of Kv4.3 and Nav1.8, and negligible expression of Kv4.2.  Furthermore, specific dominant-negative suppression and overexpression strategies confirmed the contribution of Kv4 channels to IA in DRG neurons.  Contrasting the expression patterns of Kv4 channels in the central and peripheral nervous systems, we discuss possible functional roles of these channels in primary sensory neurons.

  12. Calcium supplements

    Science.gov (United States)

    ... and over: 1,200 mg/day The body needs vitamin D to help absorb calcium. You can get ... from your diet. Ask your provider whether you need to take a vitamin D supplement. SIDE EFFECTS AND SAFETY DO NOT ...

  13. The protective role of yeast cathepsin D in acetic acid-induced apoptosis depends on ANT (Aac2p) but not on the voltage-dependent channel (Por1p).

    Science.gov (United States)

    Pereira, Helena; Azevedo, Flávio; Rego, António; Sousa, Maria João; Chaves, Susana R; Côrte-Real, Manuela

    2013-01-16

    We have previously shown that the yeast Cathepsin D (CatD) Pep4p translocates from the vacuole to the cytosol during acetic acid-induced apoptosis and is required for efficient mitochondrial degradation, though its specific role in this process is still elusive. Here, we show that the protective role of Pep4p in acetic acid-induced apoptosis depends on its catalytic activity and is independent of the yeast voltage-dependent anion channel Por1p (which has no role on mitochondrial degradation) but dependent on AAC proteins, the yeast adenine nucleotide translocator. Our results demonstrate a differential interplay between yeast vacuolar CatD and mitochondrial proteins involved in apoptosis regulation. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  14. High Cell Density Upregulates Calcium Oscillation by Increasing Calcium Store Content via Basal Mitogen-Activated Protein Kinase Activity.

    Directory of Open Access Journals (Sweden)

    Mitsuhiro Morita

    Full Text Available Calcium releases of non-excitable cells are generally a combination of oscillatory and non-oscillatory patterns, and factors affecting the calcium dynamics are still to be determined. Here we report the influence of cell density on calcium increase patterns of clonal cell lines. The majority of HeLa cells seeded at 1.5 x 104/cm2 showed calcium oscillations in response to histamine and ATP, whereas cells seeded at 0.5 x 104/cm2 largely showed transient and sustained calcium increases. Cell density also affected the response of HEK293 cells to ATP in a similar manner. High cell density increased the basal activity of the mitogen-activated protein (MAP kinase and calcium store content, and both calcium oscillation and calcium store content were down-regulated by a MAP kinase inhibitor, U0126. Thus, MAP kinase-mediated regulation of calcium store likely underlie the effect of cell density on calcium oscillation. Calcium increase patterns of HeLa cells were conserved at any histamine concentrations tested, whereas the overexpression of histamine H1 receptor, which robustly increased histamine-induced inositol phospholipid hydrolysis, converted calcium oscillations to sustained calcium increases only at high histamine concentrations. Thus, the consequence of modulating inositol phospholipid metabolism was distinct from that of changing cell density, suggesting the effect of cell density is not attributed to inositol phospholipid metabolism. Collectively, our results propose that calcium increase patterns of non-excitable cells reflect calcium store, which is regulated by the basal MAP kinase activity under the influence of cell density.

  15. Trans-channel interactions in batrachotoxin-modified skeletal muscle sodium channels: voltage-dependent block by cytoplasmic amines, and the influence of mu-conotoxin GIIIA derivatives and permeant ions.

    Science.gov (United States)

    Pavlov, Evgeny; Britvina, Tatiana; McArthur, Jeff R; Ma, Quanli; Sierralta, Iván; Zamponi, Gerald W; French, Robert J

    2008-11-01

    External mu-conotoxins and internal amine blockers inhibit each other's block of voltage-gated sodium channels. We explore the basis of this interaction by measuring the shifts in voltage-dependence of channel inhibition by internal amines induced by two mu-conotoxin derivatives with different charge distributions and net charges. Charge changes on the toxin were made at residue 13, which is thought to penetrate most deeply into the channel, making it likely to have the strongest individual interaction with an internal charged ligand. When an R13Q or R13E molecule was bound to the channel, the voltage dependence of diethylammonium (DEA)-block shifted toward more depolarized potentials (23 mV for R13Q, and 16 mV for R13E). An electrostatic model of the repulsion between DEA and the toxin simulated these data, with a distance between residue 13 of the mu-conotoxin and the DEA-binding site of approximately 15 A. Surprisingly, for tetrapropylammonium, the shifts were only 9 mV for R13Q, and 7 mV for R13E. The smaller shifts associated with R13E, the toxin with a smaller net charge, are generally consistent with an electrostatic interaction. However, the smaller shifts observed for tetrapropylammonium than for DEA suggest that other factors must be involved. Two observations indicate that the coupling of permeant ion occupancy of the channel to blocker binding may contribute to the overall amine-toxin interaction: 1), R13Q binding decreases the apparent affinity of sodium for the conducting pore by approximately 4-fold; and 2), increasing external [Na(+)] decreases block by DEA at constant voltage. Thus, even though a number of studies suggest that sodium channels are occupied by no more than one ion most of the time, measurable coupling occurs between permeant ions and toxin or amine blockers. Such interactions likely determine, in part, the strength of trans-channel, amine-conotoxin interactions.

  16. Distinct Myocardial Mechanisms Underlie Cardiac Dysfunction in Endotoxemic Male and Female Mice.

    Science.gov (United States)

    Hobai, Ion A; Aziz, Kanwal; Buys, Emmanuel S; Brouckaert, Peter; Siwik, Deborah A; Colucci, Wilson S

    2016-12-01

    In male mice, sepsis-induced cardiomyopathy develops as a result of dysregulation of myocardial calcium (Ca) handling, leading to depressed cellular Ca transients (ΔCai). ΔCai depression is partially due to inhibition of sarcoplasmic reticulum Ca ATP-ase (SERCA) via oxidative modifications, which are partially opposed by cGMP generated by the enzyme soluble guanylyl cyclase (sGC). Whether similar mechanisms underlie sepsis-induced cardiomyopathy in female mice is unknown.Male and female C57Bl/6J mice (WT), and mice deficient in the sGC α1 subunit activity (sGCα1), were challenged with lipopolysaccharide (LPS, ip). LPS induced mouse death and cardiomyopathy (manifested as the depression of left ventricular ejection fraction by echocardiography) to a similar degree in WT male, WT female, and sGCα1 male mice, but significantly less in sGCα1 female mice. We measured sarcomere shortening and ΔCai in isolated, externally paced cardiomyocytes, at 37°C. LPS depressed sarcomere shortening in both WT male and female mice. Consistent with previous findings, in male mice, LPS induced a decrease in ΔCai (to 30 ± 2% of baseline) and SERCA inhibition (manifested as the prolongation of the time constant of Ca decay, τCa, to 150 ± 5% of baseline). In contrast, in female mice, the depression of sarcomere shortening induced by LPS occurred in the absence of any change in ΔCai, or SERCA activity. This suggested that, in female mice, the causative mechanism lies downstream of the Ca transients, such as a decrease in myofilament sensitivity for Ca. The depression of sarcomere shortening shortening after LPS was less severe in female sGCα1 mice than in WT female mice, indicating that cGMP partially mediates cardiomyocyte dysfunction.These results suggest, therefore, that LPS-induced cardiomyopathy develops through distinct sex-specific myocardial mechanisms. While in males LPS induces sGC-independent decrease in ΔCai, in female mice LPS acts downstream of

  17. Calcium blood test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003477.htm Calcium blood test To use the sharing features on this page, please enable JavaScript. The calcium blood test measures the level of calcium in the blood. ...

  18. On the Frequency and Voltage-Dependent Profiles of the Surface States and Series Resistance of Au/ZnO/n-Si Structures in a Wide Range of Frequency and Voltage

    Science.gov (United States)

    Nikravan, Afsoun; Badali, Yosef; Altındal, Şemsettin; Uslu, İbrahim; Orak, İkram

    2017-10-01

    In order to interpret the electrical characteristics of fabricated Au/ZnO/n-Si structures as a function of frequency and voltage well, their capacitance-voltage ( C- V) and conductance-voltage ( G/ ω- V) measurements were carried out in a wide range of frequencies (0.7 kHz-2 MHz) and voltages (± 6 V) by 50 mV steps at room temperature. Both the C- V and G/ ω- V plots have reverse, depletion, and accumulation regions such as a metal-insulator/oxide semiconductor (MIS or MOS) structures. The values of doped-donor atoms ( N D), Fermi energy level ( E F), barrier height (ΦB), and series resistance ( R s) of the structure were obtained as a function of frequency and voltage. While the value of N D decreases with increasing frequency almost as exponentially, the value of depletion width ( W D) increases. The values of C and G/ ω increase with decreasing frequency because the surface states ( N ss) are able to follow the alternating current (AC) signal, resulting in excess capacitance ( C ex) and conductance ( G ex/ ω), which depends on their relaxation time and the frequency of the AC signal. The voltage-dependent profiles of N ss were obtained from both the high-low frequency capacitance and Hill-Colleman methods. The other important parameter R s of the structure was also obtained from the Nicollian and Brews methods as a function of voltage.

  19. Zebrafish CaV2.1 Calcium Channels Are Tailored for Fast Synchronous Neuromuscular Transmission

    Science.gov (United States)

    Naranjo, David; Wen, Hua; Brehm, Paul

    2015-01-01

    The CaV2.2 (N-type) and CaV2.1 (P/Q-type) voltage-dependent calcium channels are prevalent throughout the nervous system where they mediate synaptic transmission, but the basis for the selective presence at individual synapses still remains an open question. The CaV2.1 channels have been proposed to respond more effectively to brief action potentials (APs), an idea supported by computational modeling. However, the side-by-side comparison of CaV2.1 and CaV2.2 kinetics in intact neurons failed to reveal differences. As an alternative means for direct functional comparison we expressed zebrafish CaV2.1 and CaV2.2 α-subunits, along with their accessory subunits, in HEK293 cells. HEK cells lack calcium currents, thereby circumventing the need for pharmacological inhibition of mixed calcium channel isoforms present in neurons. HEK cells also have a simplified morphology compared to neurons, which improves voltage control. Our measurements revealed faster kinetics and shallower voltage-dependence of activation and deactivation for CaV2.1. Additionally, recordings of calcium current in response to a command waveform based on the motorneuron AP show, directly, more effective activation of CaV2.1. Analysis of calcium currents associated with the AP waveform indicate an approximately fourfold greater open probability (PO) for CaV2.1. The efficient activation of CaV2.1 channels during APs may contribute to the highly reliable transmission at zebrafish neuromuscular junctions. PMID:25650925

  20. H2O2 augments cytosolic calcium in nucleus tractus solitarii neurons via multiple voltage-gated calcium channels.

    Science.gov (United States)

    Ostrowski, Tim D; Dantzler, Heather A; Polo-Parada, Luis; Kline, David D

    2017-05-01

    Reactive oxygen species (ROS) play a profound role in cardiorespiratory function under normal physiological conditions and disease states. ROS can influence neuronal activity by altering various ion channels and transporters. Within the nucleus tractus solitarii (nTS), a vital brainstem area for cardiorespiratory control, hydrogen peroxide (H 2 O 2 ) induces sustained hyperexcitability following an initial depression of neuronal activity. The mechanism(s) associated with the delayed hyperexcitability are unknown. Here we evaluate the effect(s) of H 2 O 2 on cytosolic Ca 2+ (via fura-2 imaging) and voltage-dependent calcium currents in dissociated rat nTS neurons. H 2 O 2 perfusion (200 µM; 1 min) induced a delayed, slow, and moderate increase (~27%) in intracellular Ca 2+ concentration ([Ca 2+ ] i ). The H 2 O 2 -mediated increase in [Ca 2+ ] i prevailed during thapsigargin, excluding the endoplasmic reticulum as a Ca 2+ source. The effect, however, was abolished by removal of extracellular Ca 2+ or the addition of cadmium to the bath solution, suggesting voltage-gated Ca 2+ channels (VGCCs) as targets for H 2 O 2 modulation. Recording of the total voltage-dependent Ca 2+ current confirmed H 2 O 2 enhanced Ca 2+ entry. Blocking VGCC L, N, and P/Q subtypes decreased the number of cells and their calcium currents that respond to H 2 O 2 The number of responder cells to H 2 O 2 also decreased in the presence of dithiothreitol, suggesting the actions of H 2 O 2 were dependent on sulfhydryl oxidation. In summary, here, we have shown that H 2 O 2 increases [Ca 2+ ] i and its Ca 2+ currents, which is dependent on multiple VGCCs likely by oxidation of sulfhydryl groups. These processes presumably contribute to the previously observed delayed hyperexcitability of nTS neurons in in vitro brainstem slices. Copyright © 2017 the American Physiological Society.

  1. Calcium D-saccharate

    DEFF Research Database (Denmark)

    Garcia, André Castilho; Hedegaard, Martina Vavrusova; Skibsted, Leif Horsfelt

    2016-01-01

    -saccharate becomes spontaneously supersaturated with both d-gluconate and d-saccharate calcium salts, from which only calcium d-saccharate slowly precipitates. Calcium d-saccharate is suggested to act as a stabilizer of supersaturated solutions of other calcium hydroxycarboxylates with endothermic complex formation......Molar conductivity of saturated aqueous solutions of calcium d-saccharate, used as a stabilizer of beverages fortified with calcium d-gluconate, increases strongly upon dilution, indicating complex formation between calcium and d-saccharate ions, for which, at 25 °C, Kassoc = 1032 ± 80, ΔHassoc...

  2. Nuclear calcium signalling in the regulation of brain function.

    Science.gov (United States)

    Bading, Hilmar

    2013-09-01

    Synaptic activity initiates biochemical processes that have various outcomes, including the formation of memories, increases in neuronal survival and the development of chronic pain and addiction. Virtually all activity-induced, long-lasting adaptations of brain functions require a dialogue between synapses and the nucleus that results in changes in gene expression. Calcium signals that are induced by synaptic activity and propagate into the nucleus are a major route for synapse-to-nucleus communication. Recent findings indicate that diverse forms of neuroadaptation require calcium transients in the nucleus to switch on the necessary genomic programme. Deficits in nuclear calcium signalling as a result of a reduction in synaptic activity or increased extrasynaptic NMDA receptor signalling may underlie the aetiologies of various diseases, including neurodegeneration and cognitive dysfunction.

  3. Calcium Channel Blockers

    Science.gov (United States)

    ... conditions, such as Raynaud's disease For people of African heritage and older people, calcium channel blockers might ... high-blood-pressure/in-depth/calcium-channel-blockers/ART-20047605 . Mayo Clinic Footer Legal Conditions and Terms ...

  4. Calcium and Mitosis

    Science.gov (United States)

    Hepler, P.

    1983-01-01

    Although the mechanism of calcium regulation is not understood, there is evidence that calcium plays a role in mitosis. Experiments conducted show that: (1) the spindle apparatus contains a highly developed membrane system that has many characteristics of sarcoplasmic reticulum of muscle; (2) this membrane system contains calcium; and (3) there are ionic fluxes occurring during mitosis which can be seen by a variety of fluorescence probes. Whether the process of mitosis can be modulated by experimentally modulating calcium is discussed.

  5. [Effect of tanshinone IIA on the change of calcium current induced by beta-amyloid protein 25-35 in neurons of nucleus basalis of Meynert].

    Science.gov (United States)

    Zhu, Shujuan; Qian, Yihua; Shi, Lili; Yang, Weina; Feng, Xinzheng; Li, Cuiqin; Liu, Yong

    2010-08-01

    To explore the effect of tanshinone IIA (TanIIA) on calcium current induced by beta-amyloid protein 25-35 (Abeta25-35) in neurons of nucleus basalis of Meynert (nbM). Cell acute dissociated technique and the whole-cell recording model of patch-clamp technique of single-cell were used. The voltage-dependent calcium current in neurons of nbM was recorded in SD rats first. Then the effect of TanIIA on the voltage-dependent calcium current in the neurons was assayed. The change of calcium current induced by Abeta25-35 as well as the effect of TanIIA on the change of calcium current induced by Abeta25-35 in neurons of nbM were analyzed. Extracellular fluid containing different concentrations of TanIIA was irrigated, respectively. The peak current did not change obviously. There was no difference in current density between the TanIIA group and the control group at 0 mV (P>0.05). Extracellular fluid containing 200 nmol/L Abeta25-35 was irrigated after the normal calcium current recorded under whole patch clamp, and the peak current changed obviously. There was distinct difference in the current density between the Abeta group and the control group at 0 mV (Pcalcium current was recorded under whole patch clamp, respectively, and the peak current did not change. There was no difference in current density between the TanIIA +Abeta group and the control group at 0 mV (P>0.05). In vitro, TanIIA could inhibit the calcium current amplification induced by Abeta25-35 in neurons of nbM. TanIIA may protect neurons against the toxicity of Abeta and decrease the inward flow of Ca(2+).

  6. Calcium - Function and effects

    NARCIS (Netherlands)

    Liang, Jianfen; He, Yifan; Gao, Qian; Wang, Xuan; Nout, M.J.R.

    2016-01-01

    Rice is the primary food source for more than half of the world population. Levels of calcium contents and inhibitor - phytic acid are summarized in this chapter. Phytic acid has a very strong chelating ability and it is the main inhibit factor for calcium in rice products. Calcium contents in

  7. Calcium, An Overview-1989.

    Science.gov (United States)

    Wiercinski, Floyd J

    1989-06-01

    An overview of calcium is presented including introduction, pre-history, chronology of the research recorded in the literature, discussion, summary, recent references, literature cited, acknowledgments, and appendix. Elemental calcium began with the Earth's formation. Calcium was used for utilitarian purposes in B.C. times. In the 12th and 13th centuries A.D., calcium oxide was formed by roasting limestone to form calcium carbonate. A test for calcium was found in the 17th century, and "stones" were observed in humans (see appendix). In the 19th century, calcium was isolated and chemically identified by electrolysis, and later in that century calcium was found to be needed in a physiological solution similar to the ionic content of blood. In the 20th century it was found that, in the absence of calcium, living cells pulled away from one another. Anesthesia was produced by massive injection of magnesium salts into a mammal-conciousness could be restored by the addition of calcium, which neutralized the magnesium. Finally, calcium out of control in necrosis has an invasive action. Calcium antagonists and their mode of action were described in 1986.

  8. Effect of HeNe laser on calcium signals in sperm cells

    Science.gov (United States)

    Lubart, Rachel; Friedmann, Harry; Cohen, Natalie; Brietbart, Haim

    1998-12-01

    Irradiation of mouse spermatozoa by 630 nm HeNe laser was found to enhance calcium transport in these cells. The change in Ca transport was investigated through two approaches, the first employing the fluorescent Ca indicator, Fluo-3 AM and a fluorescence microscopic system, and the second the radiolabeled Ca uptake. In both approaches the effect of light on Ca transport was abrogated in the absence of Ca during the irradiation time, indicating that the effect of light is Ca-dependent. The stimulatory effect of light on Ca uptake was inhibited by treatment with catalase, suggesting H2O2 to be involved in light stimulated Ca2+ uptake. The stimulatory effect of light on Ca uptake was abolished in the presence of a voltage-dependent Ca-channel inhibitor, nifedipine, indicating the involvement of a plasma membrane, voltage- dependent Ca-channel. In contrast, addition of nifedipine prior to the HeNe laser irradiation did not affect the light-induced rise in intracellular Ca levels, as measured with Fluo-3 loaded sperm cells. Therefore, it can be concluded that this Ca influx occurs via a voltage- insensitive Ca-channel. The stimulatory effect of light on Ca uptake was almost completely abolished by the mitochondrial uncoupler FCCP. These data imply that light affects the mitochondrial Ca transport mechanisms. It is well known that Ca influx from an extracellular environment is an essential component of a signaling cascade leading to fertilization.

  9. Separation of intramembrane charging components in low-calcium solutions in frog skeletal muscle.

    Science.gov (United States)

    Huang, C L

    1991-08-01

    The inactivation of charge movement components by small (-100 to -70 mV) shifts in holding potential was examined in voltage-clamped intact amphibian muscle fibers in low [Ca2+], Mg(2+)-containing solutions. The pulse protocols used both large voltage excursions and smaller potential steps that elicited prolonged (q gamma) transients. Charge species were distinguished through the pharmacological effects of tetracaine. These procedures confirmed earlier observations in cut fibers and identified the following new properties of the q gamma charge. First, q gamma, previously defined as the tetracaine-sensitive charge, is also the component primarily responsible for the voltage-dependent inactivation induced by conditions of low extracellular [Ca2+]. Second, this inactivation separates a transient that includes a "hump" component and which has kinetics and a voltage dependence distinct from the monotonic decay that remains. Third, q gamma, previously associated with delayed charge movements, can also contribute significant charge transfer at early times. These findings suggest that the parallel inhibition of calcium signals and charge movements reported in low [Ca2+] solutions arises from influences on q gamma charge (Brum et al., 1988a, b). They also reconcile reports that implicate tetracaine-sensitive (q gamma) charge in excitation-contraction coupling with evidence that early intramembrane events are also involved in this process (Pizarro et al., 1989). Finally, they are relevant to hypotheses of possible feedback or feed-forward roles of q gamma in excitation-contraction coupling.

  10. A Korean family of hypokalemic periodic paralysis with mutation in a voltage-gated calcium channel (R1239G).

    Science.gov (United States)

    Kim, June Bum; Lee, Kyung Yil; Hur, Jae Kyun

    2005-02-01

    Hypokalemic periodic paralysis (HOPP) is a rare disease characterized by reversible attacks of muscle weakness accompanied by episodic hypokalemia. Recent molecular work has revealed that the majority of familial HOPP is due to mutations in a skeletal muscle voltage-dependent calcium-channel: the dihydropyridine receptor. We report a 13-yr old boy with HOPP from a family in which 6 members are affected in three generations. Genetic examination identified a nucleotide 3705 C to G mutation in exon 30 of the calcium channel gene, CACNA1S. This mutation predicts a codon change from arginine to glycine at the amino acid position #1239 (R1239G). Among the three known mutations of the CACNA1S gene, the R1239G mutation was rarely reported. This boy and the other family members who did not respond to acetazolamide, showed a marked improvement of the paralytic symptoms after spironolactone treatment.

  11. Effect of caffeine on intramembrane charge movement and calcium transients in cut skeletal muscle fibres of the frog.

    Science.gov (United States)

    Kovács, L; Szücs, G

    1983-08-01

    1. The authors have studied the effect of caffeine in subthreshold concentration (0.5 mmol l(-1) at 2-4 degrees C) on the contraction threshold, on intramembrane charge movement and calcium transients in voltage-clamped frog skeletal muscle fibres.2. The single-gap technique (Kovács & Schneider, 1978) was used for the voltage clamping of terminated segments of cut fibres. Ionic conductances were minimized by using caesium glutamate at the open end pool and tetraethylammonium sulphate and tetrodotoxin at the closed end pool.3. Myoplasmic calcium transients evoked by depolarizing pulses were recorded by measuring the changes in absorbance of the fibres at 720 nm after the intracellular application of Antipyrylazo III dye.4. The strength-duration curve for contraction threshold was shifted towards more negative membrane potentials in the presence of caffeine. Shift was more definite at shorter pulse durations than at the rheobase.5. The total amount of charge moving during the depolarizing pulses at different membrane potentials was not changed by caffeine treatment, whereas the threshold amounts of charge moved during the critical periods of the contraction threshold decreased at different voltages (by about 23%).6. In the presence of caffeine, calcium transients accompanying long (100 ms) depolarizing pulses showed increased voltage-dependent peak amplitudes, rising phases and rate coefficients referring to calcium release, but a decreased voltage-dependent re-uptake rate either during or after the pulse.7. Calcium transients evoked by depolarizing pulses along the strength-duration curve for contraction threshold gave the same peak amplitudes (ranging from 0.9 to 2.8 mumol l(-1) free myoplasmic calcium on different fibres), but membrane-potential-dependent latency times and rising phases. The rate coefficients for declining phase did not depend on the preceding pulse voltage.8. On applying caffeine, the calcium transients related to the contraction threshold also

  12. Calcium absorption and achlorhydria

    International Nuclear Information System (INIS)

    Recker, R.R.

    1985-01-01

    Defective absorption of calcium has been thought to exist in patients with achlorhydria. The author compared absorption of calcium in its carbonate form with that in a pH-adjusted citrate form in a group of 11 fasting patients with achlorhydria and in 9 fasting normal subjects. Fractional calcium absorption was measured by a modified double-isotope procedure with 0.25 g of calcium used as the carrier. Mean calcium absorption (+/- S.D.) in the patients with achlorhydria was 0.452 +/- 0.125 for citrate and 0.042 +/- 0.021 for carbonate (P less than 0.0001). Fractional calcium absorption in the normal subjects was 0.243 +/- 0.049 for citrate and 0.225 +/- 0.108 for carbonate (not significant). Absorption of calcium from carbonate in patients with achlorhydria was significantly lower than in the normal subjects and was lower than absorption from citrate in either group; absorption from citrate in those with achlorhydria was significantly higher than in the normal subjects, as well as higher than absorption from carbonate in either group. Administration of calcium carbonate as part of a normal breakfast resulted in completely normal absorption in the achlorhydric subjects. These results indicate that calcium absorption from carbonate is impaired in achlorhydria under fasting conditions. Since achlorhydria is common in older persons, calcium carbonate may not be the ideal dietary supplement

  13. Calcium channel blocker poisoning

    Directory of Open Access Journals (Sweden)

    Miran Brvar

    2005-04-01

    Full Text Available Background: Calcium channel blockers act at L-type calcium channels in cardiac and vascular smooth muscles by preventing calcium influx into cells with resultant decrease in vascular tone and cardiac inotropy, chronotropy and dromotropy. Poisoning with calcium channel blockers results in reduced cardiac output, bradycardia, atrioventricular block, hypotension and shock. The findings of hypotension and bradycardia should suggest poisoning with calcium channel blockers.Conclusions: Treatment includes immediate gastric lavage and whole-bowel irrigation in case of ingestion of sustainedrelease products. All patients should receive an activated charcoal orally. Specific treatment includes calcium, glucagone and insulin, which proved especially useful in shocked patients. Supportive care including the use of catecholamines is not always effective. In the setting of failure of pharmacological therapy transvenous pacing, balloon pump and cardiopulmonary by-pass may be necessary.

  14. Effects of caffeine on calcium release from the sarcoplasmic reticulum in frog skeletal muscle fibres.

    Science.gov (United States)

    Klein, M G; Simon, B J; Schneider, M F

    1990-06-01

    1. Resting myoplasmic [Ca2+] and [Ca2+] transients (delta [Ca2+]) were monitored using Fura-2 fluorescence and Antipyrylazo III absorbance signals from voltage-clamped segments of cut frog skeletal muscle fibres in the presence and absence of 0.5 mM-caffeine. The rate of release (Rrel) of calcium from the sarcoplasmic reticulum was calculated from delta [Ca2+]. 2. delta [Ca2+] and Rrel were increased in caffeine for all pulses. The decline of delta [Ca2+] was slower after a given pulse in caffeine than without caffeine. Resting [Ca2+] was slightly elevated in caffeine. 3. The voltage dependence of the peak value of Rrel and of the steady level of Rrel at the end of a 60-120 ms pulse were both shifted towards more negative voltages in caffeine. For relatively small pulses the voltage at which a given release waveform was observed was also shifted to more negative voltages. 4. Intramembrane charge movements measured in the same fibres in which the above changes in Rrel were observed showed no significant changes in caffeine. 5. In caffeine calcium release continued for many milliseconds after the end of a short (10 ms) pulse. Continued release after a pulse was not observed without caffeine and was probably due to positive feedback of elevated [Ca2+] on calcium release resulting from calcium-induced calcium release in caffeine. 6. Intramembrane charge movements after short pulses showed no change in caffeine that could account for the continued calcium release after the pulse. 7. Continued release after short pulses in caffeine decreased as the pulse duration was increased and was absent for pulses of 60 ms or longer. Rrel also inactivated during such pulses. 8. Relatively large and long conditioning pulses in caffeine suppressed both the peak Rrel and the continued release after short pulses. Peak release and continued release after short pulses recovered in parallel with increasing recovery time following suppression by a conditioning pulse in caffeine. 9. These

  15. Dengue and Calcium

    OpenAIRE

    Shivanthan, Mitrakrishnan C; Rajapakse, Senaka

    2014-01-01

    Dengue is potentially fatal unless managed appropriately. No specific treatment is available and the mainstay of treatment is fluid management with careful monitoring, organ support, and correction of metabolic derangement. Evidence with regards to the role of calcium homeostasis in dengue is limited. Low blood calcium levels have been demonstrated in dengue infection and hypocalcemia maybe more pronounced in more severe forms. The cause of hypocalcemia is likely to be multifactorial. Calcium...

  16. Functional characterization of acetylcholine receptors and calcium signaling in rat testicular capsule contraction.

    Science.gov (United States)

    da Silva Júnior, Edilson Dantas; de Souza, Bruno Palmieri; Rodrigues, Juliano Quintela Dantas; Caricati-Neto, Afonso; Jurkiewicz, Aron; Jurkiewicz, Neide Hyppolito

    2013-08-15

    The motor activity of mammalian testicular capsule (TC) contributes to male fertility and infertility, but the acetylcholine receptors related to the contractions induced by cholinergic drugs are poorly known. Indeed to characterize the acetylcholine receptors and cellular signaling by Ca(2+) involved in TC motor activity of rats, the potency of agonists (pD₂) and antagonists (pA₂) of acetylcholine receptors, and effects of Ca(2+) cellular transport blockers on the cholinergic contractions were evaluated. pD₂ values of acetylcholine (5.98) were ten-fold higher than that of carbachol (4.99). Efficacy (Emax) of acetylcholine and carbachol to induce contractions corresponded to 95% and 97% of Emax for KCl, but Emax for nicotine was very low (8% of Emax for KCl). Further, physostigmine did not affect the acetylcholine potency. Contractions induced by acetylcholine or carbachol were antagonized by muscarinic but not nicotinic antagonist. The order of pA₂ values obtained for muscarinic antagonists, namely atropine>4-DAMP>AF-DX116>pirenzepine, corresponded to a typical profile of M3 receptors. Contractions induced by acetylcholine or carbachol were inhibited by blockers of Ca(2+) influx through voltage-dependent calcium channels (nifedipine and Ni(2+)), Ca(2+) reuptake by sarco-endoplasmic reticulum (cyclopiazonic acid) and mitochondria (FCCP). The protein kinase C (PKC) inhibitor chelerythrine only affected the acetylcholine-induced contraction. These results suggest that TC motor activity of rats are mediated mainly by M₃ receptors followed by the increase of cytosolic Ca(2+) concentration regulated by voltage-dependent calcium channels, sarco-endoplasmic reticulum and mitochondria. Furthermore, the differential effects of chelerythrine in the acetylcholine or carbachol-induced contractions are discussed. © 2013 Elsevier B.V. All rights reserved.

  17. Calcium signaling in neurodegeneration

    Directory of Open Access Journals (Sweden)

    Dreses-Werringloer Ute

    2009-05-01

    Full Text Available Abstract Calcium is a key signaling ion involved in many different intracellular and extracellular processes ranging from synaptic activity to cell-cell communication and adhesion. The exact definition at the molecular level of the versatility of this ion has made overwhelming progress in the past several years and has been extensively reviewed. In the brain, calcium is fundamental in the control of synaptic activity and memory formation, a process that leads to the activation of specific calcium-dependent signal transduction pathways and implicates key protein effectors, such as CaMKs, MAPK/ERKs, and CREB. Properly controlled homeostasis of calcium signaling not only supports normal brain physiology but also maintains neuronal integrity and long-term cell survival. Emerging knowledge indicates that calcium homeostasis is not only critical for cell physiology and health, but also, when deregulated, can lead to neurodegeneration via complex and diverse mechanisms involved in selective neuronal impairments and death. The identification of several modulators of calcium homeostasis, such as presenilins and CALHM1, as potential factors involved in the pathogenesis of Alzheimer's disease, provides strong support for a role of calcium in neurodegeneration. These observations represent an important step towards understanding the molecular mechanisms of calcium signaling disturbances observed in different brain diseases such as Alzheimer's, Parkinson's, and Huntington's diseases.

  18. DIHYDROPYRIDINE CALCIUM- CHANNELBLOCKERSFOR ...

    African Journals Online (AJOL)

    and degenerative dementias the calcium-channel blocker nimodipine, compared with placebo, slightly improved the. MMSE scores." Thus, an additional or alternative explanation, albeit still unproven, could involve specific neuroprotection conferred by calcium-channel blockade.~Indeed, the ageing brain loses its ability to ...

  19. Calcium channel blocker overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002580.htm Calcium-channel blocker overdose To use the sharing features on this ... vary. However, the main ingredient is called a calcium-channel antagonist. It helps decrease the heart's pumping strength, which ...

  20. Extracellular Calcium and Magnesium

    African Journals Online (AJOL)

    ABSTRACT. The cause of preeclampsia remains unknown and calcium and magnesium supplement are being suggested as means of prevention. The objective of this study was to assess magnesium and calcium in the plasma and cerebrospinal fluid of Nigerian women with preedamp sia and eclampsia. Setting was ...

  1. Calcium and bones

    Science.gov (United States)

    ... eat in their diet. Vitamin D is the hormone that helps the gut absorb more calcium. Many older adults have common risks that make bone health worse. Calcium intake in the diet (milk, cheese, yogurt) is low. Vitamin D levels are ...

  2. Recreational stimulants, herbal, and spice cannabis: The core psychobiological processes that underlie their damaging effects.

    Science.gov (United States)

    Parrott, Andrew C; Hayley, Amie C; Downey, Luke A

    2017-05-01

    Recreational drugs are taken for their positive mood effects, yet their regular usage damages well-being. The psychobiological mechanisms underlying these damaging effects will be debated. The empirical literature on recreational cannabinoids and stimulant drugs is reviewed. A theoretical explanation for how they cause similar types of damage is outlined. All psychoactive drugs cause moods and psychological states to fluctuate. The acute mood gains underlie their recreational usage, while the mood deficits on withdrawal explain their addictiveness. Cyclical mood changes are found with every central nervous system stimulant and also occur with cannabis. These mood state changes provide a surface index for more profound psychobiological fluctuations. Homeostatic balance is altered, with repetitive disturbances of the hypothalamic-pituitary-adrenal axis, and disrupted cortisol-neurohormonal secretions. Hence, these drugs cause increased stress, disturbed sleep, neurocognitive impairments, altered brain activity, and psychiatric vulnerability. Equivalent deficits occur with novel psychoactive stimulants such as mephedrone and artificial "spice" cannabinoids. These psychobiological fluctuations underlie drug dependency and make cessation difficult. Psychobiological stability and homeostatic balance are optimally restored by quitting psychoactive drugs. Recreational stimulants such as cocaine or MDMA (3.4-methylenedioxymethamphetamine) and sedative drugs such as cannabis damage human homeostasis and well-being through similar core psychobiological mechanisms. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Neural regions that underlie reinforcement learning are also active for social expectancy violations.

    Science.gov (United States)

    Harris, Lasana T; Fiske, Susan T

    2010-01-01

    Prediction error, the difference between an expected and an actual outcome, serves as a learning signal that interacts with reward and punishment value to direct future behavior during reinforcement learning. We hypothesized that similar learning and valuation signals may underlie social expectancy violations. Here, we explore the neural correlates of social expectancy violation signals along the universal person-perception dimensions trait warmth and competence. In this context, social learning may result from expectancy violations that occur when a target is inconsistent with an a priori schema. Expectancy violation may activate neural regions normally implicated in prediction error and valuation during appetitive and aversive conditioning. Using fMRI, we first gave perceivers high warmth or competence behavioral information that led to dispositional or situational attributions for the behavior. Participants then saw pictures of people responsible for the behavior; they represented social groups either inconsistent (rated low on either warmth or competence) or consistent (rated high on either warmth or competence) with the behavior information. Warmth and competence expectancy violations activate striatal regions that represent evaluative and prediction error signals. Social cognition regions underlie consistent expectations. These findings suggest that regions underlying reinforcement learning may work in concert with social cognition regions in warmth and competence social expectancy. This study illustrates the neural overlap between neuroeconomics and social neuroscience.

  4. Deficiency in the Heat Stress Response Could Underlie Susceptibility to Metabolic Disease.

    Science.gov (United States)

    Rogers, Robert S; Morris, E Matthew; Wheatley, Joshua L; Archer, Ashley E; McCoin, Colin S; White, Kathleen S; Wilson, David R; Meers, Grace M E; Koch, Lauren G; Britton, Steven L; Thyfault, John P; Geiger, Paige C

    2016-11-01

    Heat treatment (HT) effectively prevents insulin resistance and glucose intolerance in rats fed a high-fat diet (HFD). The positive metabolic actions of heat shock protein 72 (HSP72), which include increased oxidative capacity and enhanced mitochondrial function, underlie the protective effects of HT. The purpose of this study was to test the ability of HSP72 induction to mitigate the effects of consumption of a short-term 3-day HFD in rats selectively bred to be low-capacity runners (LCRs) and high-capacity runners (HCRs)-selective breeding that results in disparate differences in intrinsic aerobic capacity. HCR and LCR rats were fed a chow or HFD for 3 days and received a single in vivo HT (41°C, for 20 min) or sham treatment (ST). Blood, skeletal muscles, liver, and adipose tissues were harvested 24 h after HT/ST. HT decreased blood glucose levels, adipocyte size, and triglyceride accumulation in liver and muscle and restored insulin sensitivity in glycolytic muscles from LCR rats. As expected, HCR rats were protected from the HFD. Importantly, HSP72 induction was decreased in LCR rats after only 3 days of eating the HFD. Deficiency in the highly conserved stress response mediated by HSPs could underlie susceptibility to metabolic disease with low aerobic capacity. © 2016 by the American Diabetes Association.

  5. Chemical analysis and calcium channel blocking activity of the essential oil of Perovskia abrotanoides.

    Science.gov (United States)

    Shah, Abdul Jabbar; Rasheed, Munawwer; Jabeen, Qaiser; Ahmed, Amir; Tareen, Rasool Bakhsh; Gilani, Anwarul Hassan; Nadir, Muhammad; Ahmad, Viqar Uddin

    2013-11-01

    The aim of this study was to investigate the chemical composition and provide a pharmacological base for the medicinal use of the essential oil of Perovskia abrotanoides (Pa.Oil) in gastrointestinal disorders, such as colic. The chemical investigation resulted in the identification of 26 compounds, of which tricyclene, beta-trans-ocimene, terpinene-4-acetate, terpinen-4-ol, caran-3beta-ol, linalyl acetate, beta-caryophyllene oxide and alpha-elemene had not previously been reported from P. abrotanoides. Major constituents were 1,8-cineol and delta-3-carene, which constituting 50% of the oil. In the isolated rabbit jejunum preparation Pa.Oil caused inhibition of spontaneous and high K+ (80 mM)-induced contractions, with respective EC50 values of 0.13 (0.08-0.20; n = 4) and 0.90 mg/mL (0.50-1.60; n = 5), thus showing that spasmolytic activity is mediated possibly through calcium channel blockade (CCB). The CCB activity was confirmed when pre-treatment of the tissue with Pa.Oil (0.03-0.1 mg/mL) caused a rightward shift in the Ca++ concentration-response curves, similar to that caused by verapamil, a standard calcium channel blocker. These data indicate that the essential oil of P. abrotanoides possesses spasmolytic activity mediated possibly through inhibition of voltage-dependent calcium channels, which may explain its medicinal use in colic and possibly diarrhea.

  6. Local calcium elevation and cell elongation initiate guided motility in electrically stimulated osteoblast-like cells.

    Directory of Open Access Journals (Sweden)

    Nurdan Ozkucur

    Full Text Available BACKGROUND: Investigation of the mechanisms of guided cell migration can contribute to our understanding of many crucial biological processes, such as development and regeneration. Endogenous and exogenous direct current electric fields (dcEF are known to induce directional cell migration, however the initial cellular responses to electrical stimulation are poorly understood. Ion fluxes, besides regulating intracellular homeostasis, have been implicated in many biological events, including regeneration. Therefore understanding intracellular ion kinetics during EF-directed cell migration can provide useful information for development and regeneration. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the initial events during migration of two osteogenic cell types, rat calvarial and human SaOS-2 cells, exposed to strong (10-15 V/cm and weak (< or = 5 V/cm dcEFs. Cell elongation and perpendicular orientation to the EF vector occurred in a time- and voltage-dependent manner. Calvarial osteoblasts migrated to the cathode as they formed new filopodia or lamellipodia and reorganized their cytoskeleton on the cathodal side. SaOS-2 cells showed similar responses except towards the anode. Strong dcEFs triggered a rapid increase in intracellular calcium levels, whereas a steady state level of intracellular calcium was observed in weaker fields. Interestingly, we found that dcEF-induced intracellular calcium elevation was initiated with a local rise on opposite sides in calvarial and SaOS-2 cells, which may explain their preferred directionality. In calcium-free conditions, dcEFs induced neither intracellular calcium elevation nor directed migration, indicating an important role for calcium ions. Blocking studies using cadmium chloride revealed that voltage-gated calcium channels (VGCCs are involved in dcEF-induced intracellular calcium elevation. CONCLUSION/SIGNIFICANCE: Taken together, these data form a time scale of the morphological and physiological

  7. Protecting the Innocence of Youth: Moral Sanctity Values Underlie Censorship From Young Children.

    Science.gov (United States)

    Anderson, Rajen A; Masicampo, E J

    2017-11-01

    Three studies examined the relationship between people's moral values (drawing on moral foundations theory) and their willingness to censor immoral acts from children. Results revealed that diverse moral values did not predict censorship judgments. It was not the case that participants who valued loyalty and authority, respectively, sought to censor depictions of disloyal and disobedient acts. Rather, censorship intentions were predicted by a single moral value-sanctity. The more people valued sanctity, the more willing they were to censor from children, regardless of the types of violations depicted (impurity, disloyalty, disobedience, etc.). Furthermore, people who valued sanctity objected to indecent exposure only to apparently innocent and pure children-those who were relatively young and who had not been previously exposed to immoral acts. These data suggest that sanctity, purity, and the preservation of innocence underlie intentions to censor from young children.

  8. Calcium and Vitamin D

    Science.gov (United States)

    ... by supporting muscles needed to avoid falls. Children need vitamin D to build strong bones, and adults need ... be taken at one time. While your body needs vitamin D to absorb calcium, you do not need ...

  9. High Blood Calcium (Hypercalcemia)

    Science.gov (United States)

    ... kidney function and levels of calcium in your urine. Your provider may do other tests to further assess your condition, such as checking your blood levels of phosphorus (a mineral). Imaging studies also may be helpful, ...

  10. Calcium hydroxide poisoning

    Science.gov (United States)

    Hydrate - calcium; Lime milk; Slaked lime ... thousands of construction products, flooring strippers, brick cleaners, cement thickening products, and many others) Many hair relaxers and straighteners Slaked lime This list may not include all sources of ...

  11. Calcium binding by dietary fibre

    International Nuclear Information System (INIS)

    James, W.P.T.; Branch, W.J.; Southgate, D.A.T.

    1978-01-01

    Dietary fibre from plants low in phytate bound calcium in proportion to its uronic-acid content. This binding by the non-cellulosic fraction of fibre reduces the availability of calcium for small-intestinal absorption, but the colonic microbial digestion of uronic acids liberates the calcium. Thus the ability to maintain calcium balance on high-fibre diets may depend on the adaptive capacity on the colon for calcium. (author)

  12. [Calcium suppletion for patients who use gastric acid inhibitors: calcium citrate or calcium carbonate?].

    NARCIS (Netherlands)

    Jonge, H.J. de; Gans, R.O.; Huls, G.A.

    2012-01-01

    Various calcium supplements are available for patients who have an indication for calcium suppletion. American guidelines and UpToDate recommend prescribing calcium citrate to patients who use antacids The rationale for this advice is that water-insoluble calcium carbonate needs acid for adequate

  13. Calcium in plant cells

    Directory of Open Access Journals (Sweden)

    V. V. Schwartau

    2014-04-01

    Full Text Available The paper gives the review on the role of calcium in many physiological processes of plant organisms, including growth and development, protection from pathogenic influences, response to changing environmental factors, and many other aspects of plant physiology. Initial intake of calcium ions is carried out by Ca2+-channels of plasma membrane and they are further transported by the xylem owing to auxins’ attractive ability. The level of intake and selectivity of calcium transport to ove-ground parts of the plant is controlled by a symplast. Ca2+enters to the cytoplasm of endoderm cells through calcium channels on the cortical side of Kaspary bands, and is redistributed inside the stele by the symplast, with the use of Ca2+-АТPases and Ca2+/Н+-antiports. Owing to regulated expression and activity of these calcium transporters, calclum can be selectively delivered to the xylem. Important role in supporting calcium homeostasis is given to the vacuole which is the largest depo of calcium. Regulated quantity of calcium movement through the tonoplast is provided by a number of potential-, ligand-gated active transporters and channels, like Ca2+-ATPase and Ca2+/H+ exchanger. They are actively involved in the inactivation of the calcium signal by pumping Ca2+ to the depo of cells. Calcium ATPases are high affinity pumps that efficiently transfer calcium ions against the concentration gradient in their presence in the solution in nanomolar concentrations. Calcium exchangers are low affinity, high capacity Ca2+ transporters that are effectively transporting calcium after raising its concentration in the cell cytosol through the use of protons gradients. Maintaining constant concentration and participation in the response to stimuli of different types also involves EPR, plastids, mitochondria, and cell wall. Calcium binding proteins contain several conserved sequences that provide sensitivity to changes in the concentration of Ca2+ and when you

  14. Rat hippocampal alterations could underlie behavioral abnormalities induced by exposure to moderate noise levels.

    Science.gov (United States)

    Uran, S L; Aon-Bertolino, M L; Caceres, L G; Capani, F; Guelman, L R

    2012-08-30

    Noise exposure is known to affect auditory structures in living organisms. However, it should not be ignored that many of the effects of noise are extra-auditory. Previous findings of our laboratory demonstrated that noise was able to induce behavioral alterations that are mainly related to the cerebellum (CE) and the hippocampus (HC). Therefore, the aim of this work was to reveal new data about the vulnerability of developing rat HC to moderate noise levels through the assessment of potential histological changes and hippocampal-related behavioral alterations. Male Wistar rats were exposed to noise (95-97 dB SPL, 2h daily) either for 1 day (acute noise exposure, ANE) or between postnatal days 15 and 30 (sub-acute noise exposure, SANE). Hippocampal histological evaluation as well as short (ST) and long term (LT) habituation and recognition memory assessments were performed. Results showed a mild disruption in the different hippocampal regions after ANE and SANE schemes, along with significant behavioral abnormalities. These data suggest that exposure of developing rats to noise levels of moderate intensity is able to trigger changes in the HC, an extra-auditory structure of the Central Nervous System (CNS), that could underlie the observed behavioral effects. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Chronic activation of the innate immune system may underlie the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Bruce Bartholow Duncan

    2001-05-01

    Full Text Available CONTEXTO: The metabolic syndrome is characterized by a clustering, in free-living populations, of cardiovascular and diabetes risk factors generally linked to insulin resistance, obesity and central obesity. Consonant with the well-established inflammatory pathogenesis of atherosclerotic disease, the metabolic syndrome is now being investigated in relation to its inflammatory nature. OBJETIVO: We present cross-sectional findings demonstrating that markers of inflammation correlate with components of the metabolic syndrome, and prospective findings of the ARIC Study indicating that markers of inflammation and endothelial dysfunction predict the development of diabetes mellitus and weight gain in adults. We present biological evidence to suggest that chronic activation of the innate immune system may underlie the metabolic syndrome, characterizing the common soil for the causality of type 2 diabetes mellitus and cardiovascular disease. CONCLUSIONS: Better understanding of the role of the innate immune system in these diseases may lead to important advances in the prediction and management of diabetes and cardiovascular disease.

  16. Low striatal glutamate levels underlie cognitive decline in the elderly: evidence from in vivo molecular spectroscopy.

    Science.gov (United States)

    Zahr, Natalie M; Mayer, Dirk; Pfefferbaum, Adolf; Sullivan, Edith V

    2008-10-01

    Glutamate (Glu), the principal excitatory neurotransmitter of prefrontal cortical efferents, potentially mediates higher order cognitive processes, and its altered availability may underlie mechanisms of age-related decline in frontally based functions. Although animal studies support a role for Glu in age-related cognitive deterioration, human studies, which require magnetic resonance spectroscopy for in vivo measurement of this neurotransmitter, have been impeded because of the similarity of Glu's spectroscopic signature to those of neighboring spectral brain metabolites. Here, we used a spectroscopic protocol, optimized for Glu detection, to examine the effect of age in 3 brain regions targeted by cortical efferents--the striatum, cerebellum, and pons--and to test whether performance on frontally based cognitive tests would be predicted by regional Glu levels. Healthy elderly men and women had lower Glu in the striatum but not pons or cerebellum than young adults. In the combined age groups, levels of striatal Glu (but no other proton metabolite also measured) correlated selectively with performance on cognitive tests showing age-related decline. The selective relations between performance and striatal Glu provide initial and novel, human in vivo support for age-related modification of Glu levels as contributing to cognitive decline in normal aging.

  17. Acute Cocaine Exposure elicits rises in calcium in Arousal Related Laterodorsal Tegmental Neurons

    DEFF Research Database (Denmark)

    Lambert, Mads; Ipsen, Theis; Kohlmeier, Kristi Anne

    2017-01-01

    Cocaine has strong reinforcing properties, which underlie its high addiction potential. Reinforcement of use of addictive drugs is associated with rises in dopamine (DA) in mesoaccumbal circuitry. Excitatory afferent input to mesoaccumbal circuitry sources from the laterodorsal tegmental nucleus...... (LDT). Chronic, systemic cocaine exposure has been shown to have cellular effects on LDT cells, but acute actions of local application have never been demonstrated. Using calcium imaging, we show that acute application of cocaine to mouse brain slices induces calcium spiking in cells of the LDT...... of synaptic DA, but via a different pharmacological action than cocaine, induced calcium spiking with similar profiles. Although large differences in spiking were not noted in an animal model associated with a heightened proclivity of acquiring addiction-related behavior, the prenatal nicotine exposed mouse...

  18. Interactions of calcium homeostasis, acetylcholine metabolism, behavior and 3, 4-diaminopyridine during aging

    International Nuclear Information System (INIS)

    Gibson, G.E.; Peterson, C.

    1986-01-01

    Acetylcholine synthesis declines with aging in both whole brain and in various brain regions. Since neither enzyme activities nor acetylcholine concentrations, accurately reflect the dynamics of the cholinergic system, in vivo acetylcholine formation was measured. Incorporation of U-C 14-glucose of 2 H 4 choline into whole brain acetylcholine decreases from 100% (3 months) in two strains of mice. The diminished synthesis is apparently not due to a lack of precursor availability because U- C 14-glucose and 2 H 4 choline entry into the brain is similar at all ages. It is shown that altered brain calcium homeostasis during aging may underlie the deficits in acetylcholine metabolism, as well as those in behavior. Diminished calcium uptake during aging parallels the decline in the calcium dependent release of acetylcholine

  19. Gravimetric Determination of Calcium as Calcium Carbonate Hydrate.

    Science.gov (United States)

    Henrickson, Charles H.; Robinson, Paul R.

    1979-01-01

    The gravimetric determination of calcium as calcium carbonate is described. This experiment is suitable for undergraduate quantitative analysis laboratories. It is less expensive than determination of chloride as silver chloride. (BB)

  20. Long-Term Synaptic Changes in Two Input Pathways into the Lateral Nucleus of the Amygdala Underlie Fear Extinction

    Science.gov (United States)

    Park, Junchol; Choi, June-Seek

    2010-01-01

    Plasticity in two input pathways into the lateral nucleus of the amygdala (LA), the medial prefrontal cortex (mPFC) and the sensory thalamus, have been suggested to underlie extinction, suppression of a previously acquired conditioned response (CR) following repeated presentations of the conditioned stimulus (CS). However, little is known about…

  1. Solar Imagery - Chromosphere - Calcium

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset consists of full-disk images of the sun in Calcium (Ca) II K wavelength (393.4 nm). Ca II K imagery reveal magnetic structures of the sun from about 500...

  2. Calcium in aardappel

    NARCIS (Netherlands)

    Velvis, H.

    2001-01-01

    Een overzicht wordt gegeven van de literatuur m.b.t. het element calcium in aardappel. Daarbij wordt gekeken naar de functie in de plant, de opname en het interne transport, en de gevolgen van tekorten voor de opbrengst en de vatbaarheid voor pathogenen

  3. Fruit Calcium: Transport and Physiology

    OpenAIRE

    Hocking, Bradleigh; Tyerman, Stephen D.; Burton, Rachel A.; Gilliham, Matthew

    2016-01-01

    Calcium has well-documented roles in plant signaling, water relations and cell wall interactions. Significant research into how calcium impacts these individual processes in various tissues has been carried out; however, the influence of calcium on fruit ripening has not been thoroughly explored. Here, we review the current state of knowledge on how calcium may impact fruit development, physical traits and disease susceptibility through facilitating developmental and stress response signaling...

  4. Acidosis and Urinary Calcium Excretion

    DEFF Research Database (Denmark)

    Alexander, R Todd; Cordat, Emmanuelle; Chambrey, Régine

    2016-01-01

    Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone...... in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis....

  5. The Plasma Membrane Calcium Pump

    Science.gov (United States)

    Rasmussen, H.

    1983-01-01

    Three aspect of cellular calcium metabolism in animal cells was discussed including the importance of the plasma membrane in calcium homeostasis, experiments dealing with the actual mechanism of the calcium pump, and the function of the pump in relationship to the mitochondria and to the function of calmodulin in the intact cell.

  6. Different evolutionary pathways underlie the morphology of wrist bones in hominoids.

    Science.gov (United States)

    Kivell, Tracy L; Barros, Anna P; Smaers, Jeroen B

    2013-10-23

    The hominoid wrist has been a focus of numerous morphological analyses that aim to better understand long-standing questions about the evolution of human and hominoid hand use. However, these same analyses also suggest various scenarios of complex and mosaic patterns of morphological evolution within the wrist and potentially multiple instances of homoplasy that would benefit from require formal analysis within a phylogenetic context.We identify morphological features that principally characterize primate - and, in particular, hominoid (apes, including humans) - wrist evolution and reveal the rate, process and evolutionary timing of patterns of morphological change on individual branches of the primate tree of life. Linear morphological variables of five wrist bones - the scaphoid, lunate, triquetrum, capitate and hamate - are analyzed in a diverse sample of extant hominoids (12 species, 332 specimens), Old World (8 species, 43 specimens) and New World (4 species, 26 specimens) monkeys, fossil Miocene apes (8 species, 20 specimens) and Plio-Pleistocene hominins (8 species, 18 specimens). Results reveal a combination of parallel and synapomorphic morphology within haplorrhines, and especially within hominoids, across individual wrist bones. Similar morphology of some wrist bones reflects locomotor behaviour shared between clades (scaphoid, triquetrum and capitate) while others (lunate and hamate) indicate clade-specific synapomorphic morphology. Overall, hominoids show increased variation in wrist bone morphology compared with other primate clades, supporting previous analyses, and demonstrate several occurrences of parallel evolution, particularly between orangutans and hylobatids, and among hominines (extant African apes, humans and fossil hominins). Our analyses indicate that different evolutionary processes can underlie the evolution of a single anatomical unit (the wrist) to produce diversity in functional and morphological adaptations across individual wrist

  7. Caffeine-Induced Suppression of GABAergic Inhibition and Calcium-Independent Metaplasticity

    Directory of Open Access Journals (Sweden)

    Masako Isokawa

    2016-01-01

    Full Text Available GABAergic inhibition plays a critical role in the regulation of neuron excitability; thus, it is subject to modulations by many factors. Recent evidence suggests the elevation of intracellular calcium ([Ca2+]i and calcium-dependent signaling molecules underlie the modulations. Caffeine induces a release of calcium from intracellular stores. We tested whether caffeine modulated GABAergic transmission by increasing [Ca2+]i. A brief local puff-application of caffeine to hippocampal CA1 pyramidal cells transiently suppressed GABAergic inhibitory postsynaptic currents (IPSCs by 73.2 ± 6.98%. Time course of suppression and the subsequent recovery of IPSCs resembled DSI (depolarization-induced suppression of inhibition, mediated by endogenous cannabinoids that require a [Ca2+]i rise. However, unlike DSI, caffeine-induced suppression of IPSCs (CSI persisted in the absence of a [Ca2+]i rise. Intracellular applications of BAPTA and ryanodine (which blocks caffeine-induced calcium release from intracellular stores failed to prevent the generation of CSI. Surprisingly, ruthenium red, an inhibitor of multiple calcium permeable/release channels including those of stores, induced metaplasticity by amplifying the magnitude of CSI independently of calcium. This metaplasticity was accompanied with the generation of a large inward current. Although ionic basis of this inward current is undetermined, the present result demonstrates that caffeine has a robust Ca2+-independent inhibitory action on GABAergic inhibition and causes metaplasticity by opening plasma membrane channels.

  8. Does aridity influence the morphology, distribution and accumulation of calcium oxalate crystals in Acacia (Leguminosae: Mimosoideae)?

    Science.gov (United States)

    Brown, Sharon L; Warwick, Nigel W M; Prychid, Christina J

    2013-12-01

    Calcium oxalate (CaOx) crystals are a common natural feature of many plant families, including the Leguminosae. The functional role of crystals and the mechanisms that underlie their deposition remain largely unresolved. In several species, the seasonal deposition of crystals has been observed. To gain insight into the effects of rainfall on crystal formation, the morphology, distribution and accumulation of calcium oxalate crystals in phyllodes of the leguminous Acacia sect. Juliflorae (Benth.) C. Moore & Betche from four climate zones along an aridity gradient, was investigated. The shapes of crystals, which include rare Rosanoffian morphologies, were constant between species from different climate zones, implying that morphology was not affected by rainfall. The distribution and accumulation of CaOx crystals, however, did appear to be climate-related. Distribution was primarily governed by vein density, an architectural trait which has evolved in higher plants in response to increasing aridity. Furthermore, crystals were more abundant in acacias from low rainfall areas, and in phyllodes containing high concentrations of calcium, suggesting that both aridity and soil calcium levels play important roles in the precipitation of CaOx. As crystal formation appears to be calcium-induced, we propose that CaOx crystals in Acacia most likely function in bulk calcium regulation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. Fruit Calcium: Transport and Physiology

    Directory of Open Access Journals (Sweden)

    Bradleigh eHocking

    2016-04-01

    Full Text Available Calcium has well-documented roles in plant signaling, water relations and cell wall interactions. Significant research into how calcium impacts these individual processes in various tissues has been carried out; however, the influence of calcium on fruit ripening has not been thoroughly explored. Here, we review the current state of knowledge on how calcium may impact fruit development, physical traits and disease susceptibility through facilitating developmental and stress response signaling, stabilizing membranes, influencing water relations and modifying cell wall properties through cross-linking of de-esterified pectins. We explore the involvement of calcium in hormone signaling integral to ripening and the physiological mechanisms behind common disorders that have been associated with fruit calcium deficiency (e.g. blossom end rot in tomatoes or bitter pit in apples. This review works towards an improved understanding of how the many roles of calcium interact to influence fruit ripening, and proposes future research directions to fill knowledge gaps. Specifically, we focus mostly on grapes and present a model that integrates existing knowledge around these various functions of calcium in fruit, which provides a basis for understanding the physiological impacts of sub-optimal calcium nutrition in grapes. Calcium accumulation and distribution in fruit is shown to be highly dependent on water delivery and cell wall interactions in the apoplasm. Localized calcium deficiencies observed in particular species or varieties can result from differences in xylem morphology, fruit water relations and pectin composition, and can cause leaky membranes, irregular cell wall softening, impaired hormonal signaling and aberrant fruit development. We propose that the role of apoplasmic calcium-pectin crosslinking, particularly in the xylem, is an understudied area that may have a key influence on fruit water relations. Furthermore, we believe that improved

  10. Fruit Calcium: Transport and Physiology.

    Science.gov (United States)

    Hocking, Bradleigh; Tyerman, Stephen D; Burton, Rachel A; Gilliham, Matthew

    2016-01-01

    Calcium has well-documented roles in plant signaling, water relations and cell wall interactions. Significant research into how calcium impacts these individual processes in various tissues has been carried out; however, the influence of calcium on fruit ripening has not been thoroughly explored. Here, we review the current state of knowledge on how calcium may impact the development, physical traits and disease susceptibility of fruit through facilitating developmental and stress response signaling, stabilizing membranes, influencing water relations and modifying cell wall properties through cross-linking of de-esterified pectins. We explore the involvement of calcium in hormone signaling integral to the physiological mechanisms behind common disorders that have been associated with fruit calcium deficiency (e.g., blossom end rot in tomatoes or bitter pit in apples). This review works toward an improved understanding of how the many roles of calcium interact to influence fruit ripening, and proposes future research directions to fill knowledge gaps. Specifically, we focus mostly on grapes and present a model that integrates existing knowledge around these various functions of calcium in fruit, which provides a basis for understanding the physiological impacts of sub-optimal calcium nutrition in grapes. Calcium accumulation and distribution in fruit is shown to be highly dependent on water delivery and cell wall interactions in the apoplasm. Localized calcium deficiencies observed in particular species or varieties can result from differences in xylem morphology, fruit water relations and pectin composition, and can cause leaky membranes, irregular cell wall softening, impaired hormonal signaling and aberrant fruit development. We propose that the role of apoplasmic calcium-pectin crosslinking, particularly in the xylem, is an understudied area that may have a key influence on fruit water relations. Furthermore, we believe that improved knowledge of the calcium

  11. Lead content of calcium supplements.

    Science.gov (United States)

    Ross, E A; Szabo, N J; Tebbett, I R

    2000-09-20

    Substantial quantities of lead have been reported in some over-the-counter calcium supplement preparations, including not only bone-meal and dolomite, but also over-the-counter natural and refined calcium carbonate formulations. Examination of this issue is warranted given recent increases in physician recommendations for calcium supplements for prevention and treatment of osteoporosis. To determine the lead content of calcium supplements and to quantify the lead exposure from popular brands of calcium in dosages used for childhood recommended daily allowance, osteoporosis, and phosphate binding in dialysis patients. Analysis of lead content in 21 formulations of nonprescription calcium carbonate (including 7 natural [ie, oyster shell] and 14 refined), 1 brand of prescription-only calcium acetate, and 1 noncalcium synthetic phosphate binder conducted in March 2000. Lead content, assayed using electrothermal atomic absorption, expressed as micrograms of lead per 800 mg/d of elemental calcium, per 1500 mg/d of calcium, and for a range of dosages for patients with renal failure. Six microg/d of lead was considered the absolute dietary limit, with no more than 1 microg/d being the goal for supplements. Four of 7 natural products had measurable lead content, amounting to approximately 1 microg/d for 800 mg/d of calcium, between 1 and 2 microg/d for 1500 mg/d of calcium, and up to 10 microg/d for renal dosages. Four of the 14 refined products had similar lead content, including up to 3 microg/d of lead in osteoporosis calcium dosages and up to 20 microg/d in high renal dosages. No lead was detected in the calcium acetate or polymer products. Lead was present even in some brand name products from major pharmaceutical companies not of natural oyster shell derivation. Despite increasingly stringent limits of lead exposure, many calcium supplement formulations contain lead and thereby may pose an easily avoidable public health concern. JAMA. 2000;284:1425-1429.

  12. Piezo- and Flexoelectric Membrane Materials Underlie Fast Biological Motors in the Ear.

    Science.gov (United States)

    Breneman, Kathryn D; Rabbitt, Richard D

    2009-01-01

    The mammalian inner ear is remarkably sensitive to quiet sounds, exhibits over 100dB dynamic range, and has the exquisite ability to discriminate closely spaced tones even in the presence of noise. This performance is achieved, in part, through active mechanical amplification of vibrations by sensory hair cells within the inner ear. All hair cells are endowed with a bundle of motile microvilli, stereocilia, located at the apical end of the cell, and the more specialized outer hair cells (OHC's) are also endowed with somatic electromotility responsible for changes in cell length in response to perturbations in membrane potential. Both hair bundle and somatic motors are known to feed energy into the mechanical vibrations in the inner ear. The biophysical origin and relative significance of the motors remains a subject of intense research. Several biological motors have been identified in hair cells that might underlie the motor(s), including a cousin of the classical ATP driven actin-myosin motor found in skeletal muscle. Hydrolysis of ATP, however, is much too slow to be viable at audio frequencies on a cycle-by-cycle basis. Heuristically, the OHC somatic motor behaves as if the OHC lateral wall membrane were a piezoelectric material and the hair bundle motor behaves as if the plasma membrane were a flexoelectric material. We propose these observations from a continuum materials perspective are literally true. To examine this idea, we formulated mathematical models of the OHC lateral wall "piezoelectric" motor and the more ubiquitous "flexoelectric" hair bundle motor. Plausible biophysical mechanisms underlying piezo- and flexoelectricity were established. Model predictions were compared extensively to the available data. The models were then applied to study the power conversion efficiency of the motors. Results show that the material properties of the complex membranes in hair cells provide them with the ability to convert electrical power available in the inner

  13. Models of calcium signalling

    CERN Document Server

    Dupont, Geneviève; Kirk, Vivien; Sneyd, James

    2016-01-01

    This book discusses the ways in which mathematical, computational, and modelling methods can be used to help understand the dynamics of intracellular calcium. The concentration of free intracellular calcium is vital for controlling a wide range of cellular processes, and is thus of great physiological importance. However, because of the complex ways in which the calcium concentration varies, it is also of great mathematical interest.This book presents the general modelling theory as well as a large number of specific case examples, to show how mathematical modelling can interact with experimental approaches, in an interdisciplinary and multifaceted approach to the study of an important physiological control mechanism. Geneviève Dupont is FNRS Research Director at the Unit of Theoretical Chronobiology of the Université Libre de Bruxelles;Martin Falcke is head of the Mathematical Cell Physiology group at the Max Delbrück Center for Molecular Medicine, Berlin;Vivien Kirk is an Associate Professor in the Depar...

  14. Calcium, essential for health

    Science.gov (United States)

    Martínez de Victoria, Emilio

    2016-07-12

    Calcium (Ca) is the most abundant mineral element in our body. It accounts for about 2% of body weight. The functions of calcium are: a) functions skeletal and b) regulatory functions. Bone consists of a protein matrix that mineralizes mainly with calcium (the most abundant), phosphate and magnesium, for it is essential an adequate dietary intake of Ca, phosphorus and vitamin D. The ionic Ca (Ca2+) is essential to maintain and / or perform different specialized functions of, virtually, all body cells cellular. Because of its important functions Ca2+ must be closely regulated, keeping plasma concentrations within narrow ranges. For this reason there is an accurate response against hypocalcemia or hypercalcemia in which the parathormone, calcitriol, calcitonin and vitamin K are involved. Ca intakes in the Spanish population are low in a significant percentage of the older adult’s population, especially in women. The main source of Ca in the diet is milk and milk derivatives. Green leafy vegetables, fruits and legumes can be important sources of Ca in a Mediterranean dietary pattern. The bioavailability of dietary Ca depends on physiological and dietary factors. Physiological include age, physiological status (gestation and lactation) Ca and vitamin D status and disease. Several studies relate Ca intake in the diet and various diseases, such as osteoporosis, cancer, cardiovascular disease and obesity.

  15. Voltage-dependent amplification of synaptic inputs in respiratory motoneurones

    DEFF Research Database (Denmark)

    Enríquez Denton, M; Wienecke, Jacob; Zhang, Mengliang

    2012-01-01

    time, the likely amplifying processes at work in respiratory motoneurones. In phrenic motoneurones, which control the most important respiratory muscle, the diaphragm, we found that the mechanism most favoured by investigations in other motoneurones, the activation of persistent inward currents via...

  16. Voltage-Dependent Intrinsic Bursting in Olfactory Bulb Golgi Cells

    Science.gov (United States)

    Pressler, R. Todd; Rozman, Peter A.; Strowbridge, Ben W.

    2013-01-01

    In the mammalian olfactory bulb (OB), local synaptic circuits modulate the evolving pattern of activity in mitral and tufted cells following olfactory sensory stimulation. GABAergic granule cells, the most numerous interneuron subtype in this brain region, have been extensively studied. However, classic studies using Golgi staining methods…

  17. Neuroinflammation alters voltage-dependent conductance in striatal astrocytes

    Science.gov (United States)

    Karpuk, Nikolay; Burkovetskaya, Maria

    2012-01-01

    Neuroinflammation has the capacity to alter normal central nervous system (CNS) homeostasis and function. The objective of the present study was to examine the effects of an inflammatory milieu on the electrophysiological properties of striatal astrocyte subpopulations with a mouse bacterial brain abscess model. Whole cell patch-clamp recordings were performed in striatal glial fibrillary acidic protein (GFAP)-green fluorescent protein (GFP)+ astrocytes neighboring abscesses at postinfection days 3 or 7 in adult mice. Cell input conductance (Gi) measurements spanning a membrane potential (Vm) surrounding resting membrane potential (RMP) revealed two prevalent astrocyte subsets. A1 and A2 astrocytes were identified by negative and positive Gi increments vs. Vm, respectively. A1 and A2 astrocytes displayed significantly different RMP, Gi, and cell membrane capacitance that were influenced by both time after bacterial exposure and astrocyte proximity to the inflammatory site. Specifically, the percentage of A1 astrocytes was decreased immediately surrounding the inflammatory lesion, whereas A2 cells were increased. These changes were particularly evident at postinfection day 7, revealing increased cell numbers with an outward current component. Furthermore, RMP was inversely modified in A1 and A2 astrocytes during neuroinflammation, and resting Gi was increased from 21 to 30 nS in the latter. In contrast, gap junction communication was significantly decreased in all astrocyte populations associated with inflamed tissues. Collectively, these findings demonstrate the heterogeneity of striatal astrocyte populations, which experience distinct electrophysiological modifications in response to CNS inflammation. PMID:22457466

  18. Gabapentin Modulates HCN4 Channel Voltage-Dependence

    Directory of Open Access Journals (Sweden)

    Han-Shen Tae

    2017-08-01

    Full Text Available Gabapentin (GBP is widely used to treat epilepsy and neuropathic pain. There is evidence that GBP can act on hyperpolarization-activated cation (HCN channel-mediated Ih in brain slice experiments. However, evidence showing that GBP directly modulates HCN channels is lacking. The effect of GBP was tested using two-electrode voltage clamp recordings from human HCN1, HCN2, and HCN4 channels expressed in Xenopus oocytes. Whole-cell recordings were also made from mouse spinal cord slices targeting either parvalbumin positive (PV+ or calretinin positive (CR+ inhibitory neurons. The effect of GBP on Ih was measured in each inhibitory neuron population. HCN4 expression was assessed in the spinal cord using immunohistochemistry. When applied to HCN4 channels, GBP (100 μM caused a hyperpolarizing shift in the voltage of half activation (V1/2 thereby reducing the currents. Gabapentin had no impact on the V1/2 of HCN1 or HCN2 channels. There was a robust increase in the time to half activation for HCN4 channels with only a small increase noted for HCN1 channels. Gabapentin also caused a hyperpolarizing shift in the V1/2 of Ih measured from HCN4-expressing PV+ inhibitory neurons in the spinal dorsal horn. Gabapentin had minimal effect on Ih recorded from CR+ neurons. Consistent with this, immunohistochemical analysis revealed that the majority of CR+ inhibitory neurons do not express somatic HCN4 channels. In conclusion, GBP reduces HCN4 channel-mediated currents through a hyperpolarized shift in the V1/2. The HCN channel subtype selectivity of GBP provides a unique tool for investigating HCN4 channel function in the central nervous system. The HCN4 channel is a candidate molecular target for the acute analgesic and anticonvulsant actions of GBP.

  19. Neuroinflammation alters voltage-dependent conductance in striatal astrocytes.

    Science.gov (United States)

    Karpuk, Nikolay; Burkovetskaya, Maria; Kielian, Tammy

    2012-07-01

    Neuroinflammation has the capacity to alter normal central nervous system (CNS) homeostasis and function. The objective of the present study was to examine the effects of an inflammatory milieu on the electrophysiological properties of striatal astrocyte subpopulations with a mouse bacterial brain abscess model. Whole cell patch-clamp recordings were performed in striatal glial fibrillary acidic protein (GFAP)-green fluorescent protein (GFP)(+) astrocytes neighboring abscesses at postinfection days 3 or 7 in adult mice. Cell input conductance (G(i)) measurements spanning a membrane potential (V(m)) surrounding resting membrane potential (RMP) revealed two prevalent astrocyte subsets. A1 and A2 astrocytes were identified by negative and positive G(i) increments vs. V(m), respectively. A1 and A2 astrocytes displayed significantly different RMP, G(i), and cell membrane capacitance that were influenced by both time after bacterial exposure and astrocyte proximity to the inflammatory site. Specifically, the percentage of A1 astrocytes was decreased immediately surrounding the inflammatory lesion, whereas A2 cells were increased. These changes were particularly evident at postinfection day 7, revealing increased cell numbers with an outward current component. Furthermore, RMP was inversely modified in A1 and A2 astrocytes during neuroinflammation, and resting G(i) was increased from 21 to 30 nS in the latter. In contrast, gap junction communication was significantly decreased in all astrocyte populations associated with inflamed tissues. Collectively, these findings demonstrate the heterogeneity of striatal astrocyte populations, which experience distinct electrophysiological modifications in response to CNS inflammation.

  20. Determination of percent calcium carbonate in calcium chromate

    International Nuclear Information System (INIS)

    Middleton, H.W.

    1979-01-01

    The precision, accuracy and reliability of the macro-combustion method is superior to the Knorr alkalimetric method, and it is faster. It also significantly reduces the calcium chromate waste accrual problem. The macro-combustion method has been adopted as the official method for determination of percent calcium carbonate in thermal battery grade anhydrous calcium chromate and percent calcium carbonate in quicklime used in the production of calcium chromate. The apparatus and procedure can be used to measure the percent carbonate in inorganic materials other than calcium chromate. With simple modifications in the basic apparatus and procedure, the percent carbon and hydrogen can be measured in many organic material, including polymers and polymeric formulations. 5 figures, 5 tables

  1. Impairment of mitochondrial calcium handling in a mtSOD1 cell culture model of motoneuron disease

    Directory of Open Access Journals (Sweden)

    Zippelius Annette

    2009-06-01

    Full Text Available Abstract Background Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons (MN in the brain stem and spinal cord. Intracellular disruptions of cytosolic and mitochondrial calcium have been associated with selective MN degeneration, but the underlying mechanisms are not well understood. The present evidence supports a hypothesis that mitochondria are a target of mutant SOD1-mediated toxicity in familial amyotrophic lateral sclerosis (fALS and intracellular alterations of cytosolic and mitochondrial calcium might aggravate the course of this neurodegenerative disease. In this study, we used a fluorescence charged cool device (CCD imaging system to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations in individual cells in an established cellular model of ALS. Results To gain insights into the molecular mechanisms of SOD1G93A associated motor neuron disease, we simultaneously monitored cytosolic and mitochondrial calcium concentrations in individual cells. Voltage – dependent cytosolic Ca2+ elevations and mitochondria – controlled calcium release mechanisms were monitored after loading cells with fluorescent dyes fura-2 and rhod-2. Interestingly, comparable voltage-dependent cytosolic Ca2+ elevations in WT (SH-SY5YWT and G93A (SH-SY5YG93A expressing cells were observed. In contrast, mitochondrial intracellular Ca2+ release responses evoked by bath application of the mitochondrial toxin FCCP were significantly smaller in G93A expressing cells, suggesting impaired calcium stores. Pharmacological experiments further supported the concept that the presence of G93A severely disrupts mitochondrial Ca2+ regulation. Conclusion In this study, by fluorescence measurement of cytosolic calcium and using simultaneous [Ca2+]i and [Ca2+]mito measurements, we are able to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations

  2. Activation of L-type calcium channel in twitch skeletal muscle fibres of the frog.

    Science.gov (United States)

    Francini, F; Bencini, C; Squecco, R

    1996-07-01

    1. The activation of the L-type calcium current (ICa) was studied in normally polarized (-100 mV) cut skeletal muscle fibres of the frog with the double Vaseline-gap voltage-clamp technique. Both external and internal solutions were Ca2+ buffered. Solutions were made in order to minimize all but the Ca2+ current. 2. The voltage-dependent components of the time course of activation were determined by two procedures: fast and slow components were evaluated by multiexponential fitting to current traces elicited by long voltage pulses (5 s) after removing inactivation; fast components were also determined by short voltage pulses having different duration (0.5-70 ms). 3. The components of deactivation were evaluated after removing the charge-movement current from the total tail current by the difference between two short (50 and 70 ms) voltage pulses to 10 mV, moving the same intramembrane charge. Two exponential components, fast and slow (time constants, 6 +/- 0.3 and 90 +/- 7 ms at -100 mV; n = 26), were found. 4. The time onset of ICa was evaluated either by multiexponential fitting to the ICa activation or by pulses of different duration to test the beginning of the 'on' and 'off' inequality. This was at about 2 ms, denoting that it was very early. 5. The time constant vs. voltage plots indicated the presence of four voltage-dependent components in the activation pathway. Various kinetic models are discussed. Models with independent transitions, like a Hodgkin-Huxley scheme, were excluded. Suitable models were a five-state sequential and a four-state cyclic with a branch scheme. The latter gave the best simulation of the data. 6. The steady-state activation curve saturated at high potentials. It had a half-voltage value of 1 +/- 0.2 mV and the opening probability was only 0.82 +/- 0.2 at 20 mV (n = 32). This result implies a larger number of functional calcium channels than was previously supposed and is in agreement with the number of dihydropyridine (DHP

  3. [Calcium--essential for everybody].

    Science.gov (United States)

    Cichosz, Grazyna; Czeczot, Hanna

    2014-06-01

    Calcium regulates majority of metabolic processes within human organism and its optimal intake decreases risk of metabolic illnesses conditioned by diet. Deficiency of calcium results in higher body max index, increase risk of insulin resistance, diabetes type 2 and osteoporosis. Diet delivering full calcium load diminished impendency of hypertension; calcium regulates tension of smooth muscles of blood vessels, limits neurotransmitters activity and also diminish hazardous activity of sodium chloride. Anticancerogenic activity of calcium results from formation insoluble bile acids and fat acids salts, and most of all, from inhibition of intestine mucosa cells hyper proliferation. Due to presence of vitamin D3, CLA, proteins and bioactive peptides emerging from them, milk is more efficient in prophylaxis of diet conditioned illnesses than calcium supplements. Efficiency of milk and dairy products in treatment of obesity, sclerosis and hypertension has been proved by DASH diet.

  4. Calcium addition in straw gasification

    DEFF Research Database (Denmark)

    Risnes, H.; Fjellerup, Jan Søren; Henriksen, Ulrik Birk

    2003-01-01

    The present work focuses on the influence of calcium addition in gasification. The inorganic¿organic element interaction as well as the detailed inorganic¿inorganic elements interaction has been studied. The effect of calcium addition as calcium sugar/molasses solutions to straw significantly...... affected the ash chemistry and the ash sintering tendency but much less the char reactivity. Thermo balance test are made and high-temperature X-ray diffraction measurements are performed, the experimental results indicate that with calcium addition major inorganic¿inorganic reactions take place very late...

  5. Laser Sintered Calcium Phosphate Bone

    National Research Council Canada - National Science Library

    Vail, Neil

    1999-01-01

    ...) technology selective laser sintering (SLS). BME has successfully implemented a pilot facility to fabricate calcium phosphate implants using anatomical data coupled with the selective laser sintering process...

  6. Calcium chromate process related investigations

    International Nuclear Information System (INIS)

    Dillard, B.M.

    1979-01-01

    A pilot plant for production of calcium chromate has been scaled up to a small production facility at the General Electric Neutron Devices Department. In preparation for this scale-up, the process and final product were studied in order to evaluate problems not considered previously. The variables and processes studied included: (1) the determination of optimum drying temperature and time for product analysis; (2) the effect of the grade of lime used as the precipitating agent on the purity of the calcium chromate; (3) product purity when calcium chromate is precipitated by the addition of ammonium chromate to slaked lime; (4) the reagents best suited for cleaning calcium chromate spills; and (5) methods for determining hydroxide ion concentration in calcium chromate. The optimum drying time for the product before analysis is four hours at 600 0 C. Gases evolved at various temperatures during the drying process were carbon dioxide and water vapor. Technical grade lime produced calcium chromate of the highest purity. Both nitric and acetic acids were efficient dissolvers of calcium chromate spills. Direct titration of hydroxide ion with sulfuric acid gave an average recovery of 93% for samples spiked with calcium hydroxide. 1 figure, 17 tables

  7. Calcium kinetics in parathyroid disease

    International Nuclear Information System (INIS)

    Dymling, J.F.

    1964-01-01

    This paper reports a study of calcium kinetics in twelve cases of parathyroid disease. The data suggest that hyperparathyroidism usually causes increased bone turnover. The study of calcium kinetics may be a valuable tool in the differential diagnosis of primary hyperparathyroidism and in evaluating treatment of secondary hyperparathyroidism. The bone turnover in one case of hypoparathyroidism was extremely low. 1 fig., 1 tab

  8. Calcium – how and why?

    Indian Academy of Sciences (India)

    Unknown

    calcium has achieved this status with a brief mention of the history of calcium research in biology. It appears that during the origin and early evolution of life the Ca2+ ion was given a ... tion and development of tissues (bone and calcareous skeleton) (Ringer and Sainsbury 1894), conduction of nerve impulse to muscle, cell ...

  9. Calcium Supplements: Do Men Need Them Too?

    Science.gov (United States)

    ... Nutrition and healthy eating Should men take calcium supplements? Answers from Katherine Zeratsky, R.D., L.D. ... healthy men don't need to take calcium supplements. Calcium is important for men for optimal bone ...

  10. Calcium, vitamin D, and your bones

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000490.htm Calcium, vitamin D, and your bones To use the sharing features ... and maintain strong bones. How Much Calcium and Vitamin D do I Need? Amounts of calcium are given ...

  11. The effect and mechanism of endothelin-1-induced intracellular free calcium in human lung adenocarcinoma cells SPC-A1

    Directory of Open Access Journals (Sweden)

    Juan ZHOU

    2008-08-01

    Full Text Available Background and objective Endothelin-1 (ET-1 is a potent mitogen involved in cell growth in human lung adenocarcinoma cells SPC-A1. The increase in intracellular free calcium ([Ca2+]i plays a great role in this process. The aim of this study is to investigate the ET-1-induced [Ca2+]i responses in SPC-A1 cells and to explore its cellular mechanism. Methods [Ca2+]i was measured by Fura-2/AM fluorescent assay. Endothelin receptors antagonists, calcium channel blockers and intracellular signal transduction blockers were used to study the underlying mechanism of ET-1-induced [Ca2+]i responses in SPC-A1 cells. Results At the concentration of 1×10-15 mol/L-1×10-8 mol/L, ET-1 caused a dose-dependent increase of [Ca2+]i in SPC-A1 cells (P0.05, a highly selective endothelin receptor B (ETBR antagonist. Depletion of extracellular Ca2+ with free Ca2+ solution and 0.1mmol/L ethyleneglycol bis (2-aminoethyl ether tetraacetic acid (EGTA or blockade of voltage dependent calcium channel with nifedipine at 1×10-6 mol/L significantly reduced the ET-1-induced increase of [Ca2+]i. The ET-1-induced (1×10-10 mol/L increase of [Ca2+]i was also significantly attenuated by U73122 at 1×10-5 mol/L (P<0.05, a phospholipase C inhibitor, and by Ryanodine at 50×10-6 mol/L. However, Staurosporine (2×10-9 mol/L, a protein kinas C inhibitor, exerted no significant effect on the ET-1-induced (1×10-10 mol/L increase of [Ca2+]i. Conclusion ET-1 elevates [Ca2+]i via activation of ETA receptor. Both phospholipase C/Ca2+ pathway and Ca2+ influx through voltage dependent Ca2+ channel activate by ETAR contribute to this process.

  12. Calcium addition in straw gasification

    DEFF Research Database (Denmark)

    Risnes, H.; Fjellerup, Jan Søren; Henriksen, Ulrik Birk

    2003-01-01

    The present work focuses on the influence of calcium addition in gasification. The inorganic¿organic element interaction as well as the detailed inorganic¿inorganic elements interaction has been studied. The effect of calcium addition as calcium sugar/molasses solutions to straw significantly...... affected the ash chemistry and the ash sintering tendency but much less the char reactivity. Thermo balance test are made and high-temperature X-ray diffraction measurements are performed, the experimental results indicate that with calcium addition major inorganic¿inorganic reactions take place very late...... in the char conversion process. Comprehensive global equilibrium calculations predicted important characteristics of the inorganic ash residue. Equilibrium calculations predict the formation of liquid salt if sufficient amounts of Ca are added and according to experiments as well as calculations calcium binds...

  13. Alternative Splicing of L-type CaV1.2 Calcium Channels: Implications in Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Zhenyu Hu

    2017-11-01

    Full Text Available L-type CaV1.2 calcium channels are the major pathway for Ca2+ influx to initiate the contraction of smooth and cardiac muscles. Alteration of CaV1.2 channel function has been implicated in multiple cardiovascular diseases, such as hypertension and cardiac hypertrophy. Alternative splicing is a post-transcriptional mechanism that expands CaV1.2 channel structures to modify function, pharmacological and biophysical property such as calcium/voltage-dependent inactivation (C/VDI, or to influence its post-translational modulation by interacting proteins such as Galectin-1. Alternative splicing has generated functionally diverse CaV1.2 isoforms that can be developmentally regulated in the heart, or under pathophysiological conditions such as in heart failure. More importantly, alternative splicing of certain exons of CaV1.2 has been reported to be regulated by splicing factors such as RNA-binding Fox-1 homolog 1/2 (Rbfox 1/2, polypyrimidine tract-binding protein (PTBP1 and RNA-binding motif protein 20 (RBM20. Understanding how CaV1.2 channel function is remodelled in disease will provide better information to guide the development of more targeted approaches to discover therapeutic agents for cardiovascular diseases.

  14. Gynura procumbens Merr. decreases blood pressure in rats by vasodilatation via inhibition of calcium channels

    Directory of Open Access Journals (Sweden)

    See-Ziau Hoe

    2011-01-01

    Full Text Available INTRODUCTION: Gynura procumbens has been shown to decrease blood pressure via inhibition of the angiotensinconverting enzyme. However, other mechanisms that may contribute to the hypotensive effect have not been studied. OBJECTIVES: To investigate the cardiovascular effects of a butanolic fraction of Gynura procumbens in rats. METHODS: Anaesthetized rats were given intravenous bolus injections of butanolic fraction at doses of 2.5-20 mg/kg in vivo. The effect of butanolic fraction on vascular reactivity was recorded in isolated rat aortic rings in vitro. RESULTS: Intravenous administrations of butanolic fraction elicited significant (p<0.001 and dose-dependent decreases in the mean arterial pressure. However, a significant (p<0.05 decrease in the heart rate was observed only at the higher doses (10 and 20 mg/kg. In isolated preparations of rat aortic rings, phenylephrine (1×10-6 M- or potassium chloride (8×10-2 M-precontracted endothelium-intact and -denuded tissue; butanolic fraction (1×10-6-1×10-1 g/ml induced similar concentration-dependent relaxation of the vessels. In the presence of 2.5×10-3 and 5.0×10-3 g/ml butanolic fraction, the contractions induced by phenylephrine (1×10-9-3×10-5 M and potassium chloride (1×10-2-8×10-2 M were significantly antagonized. The calcium-induced vasocontractions (1×10-4-1×10-2 M were antagonized by butanolic fraction concentration-dependently in calcium-free and high potassium (6×10-2 M medium, as well as in calcium- and potassium-free medium containing 1×10-6 M phenylephrine. However, the contractions induced by noradrenaline (1×10-6 M and caffeine (4.5×10-2 M were not affected by butanolic fraction. CONCLUSION: Butanolic fraction contains putative hypotensive compounds that appear to inhibit calcium influx via receptor-operated and/or voltage-dependent calcium channels to cause vasodilation and a consequent fall in blood pressure.

  15. Cholesterol influences voltage-gated calcium channels and BK-type potassium channels in auditory hair cells.

    Directory of Open Access Journals (Sweden)

    Erin K Purcell

    Full Text Available The influence of membrane cholesterol content on a variety of ion channel conductances in numerous cell models has been shown, but studies exploring its role in auditory hair cell physiology are scarce. Recent evidence shows that cholesterol depletion affects outer hair cell electromotility and the voltage-gated potassium currents underlying tall hair cell development, but the effects of cholesterol on the major ionic currents governing auditory hair cell excitability are unknown. We investigated the effects of a cholesterol-depleting agent (methyl beta cyclodextrin, MβCD on ion channels necessary for the early stages of sound processing. Large-conductance BK-type potassium channels underlie temporal processing and open in a voltage- and calcium-dependent manner. Voltage-gated calcium channels (VGCCs are responsible for calcium-dependent exocytosis and synaptic transmission to the auditory nerve. Our results demonstrate that cholesterol depletion reduced peak steady-state calcium-sensitive (BK-type potassium current by 50% in chick cochlear hair cells. In contrast, MβCD treatment increased peak inward calcium current (~30%, ruling out loss of calcium channel expression or function as a cause of reduced calcium-sensitive outward current. Changes in maximal conductance indicated a direct impact of cholesterol on channel number or unitary conductance. Immunoblotting following sucrose-gradient ultracentrifugation revealed BK expression in cholesterol-enriched microdomains. Both direct impacts of cholesterol on channel biophysics, as well as channel localization in the membrane, may contribute to the influence of cholesterol on hair cell physiology. Our results reveal a new role for cholesterol in the regulation of auditory calcium and calcium-activated potassium channels and add to the growing evidence that cholesterol is a key determinant in auditory physiology.

  16. Calcium Impact on Milk Gels Formation

    DEFF Research Database (Denmark)

    Koutina, Glykeria

    salts. The perturbation of calcium equilibria by these factors will affect the final properties of acid, calcium and rennet milk gels. By decreasing the pH from 6.0 to 5.2 (acid gels), the calcium equilibrium was significantly affected by temperature (4, 20, 30, 40 oC), and different combinations...... enriched dairy products. Calcium gels can be produced by addition of a calcium salt and heat treatment at temperatures higher than 70 oC for several minutes. The combination of heat treatment and calcium addition to milk with pH values between 6.6 and 5.6, will produce calcium milk gels with unique...... to be formed. In addition the low amount of micellar calcium caused a more compact gel structure with many protein aggregates. The results of this study highlighted the importance of calcium for the formation of acid, calcium and rennet gels. The content and the interactions of calcium with proteins during...

  17. Calcium signals in olfactory neurons.

    Science.gov (United States)

    Tareilus, E; Noé, J; Breer, H

    1995-11-09

    Laser scanning confocal microscopy in combination with the fluorescent calcium indicators Fluo-3 and Fura-Red was employed to estimate the intracellular concentration of free calcium ions in individual olfactory receptor neurons and to monitor temporal and spatial changes in the Ca(2+)-level upon stimulation. The chemosensory cells responded to odorants with a significant increase in the calcium concentration, preferentially in the dendritic knob. Applying various stimulation paradigma, it was found that in a population of isolated cells, subsets of receptor neurons display distinct patterns of responsiveness.

  18. Influence of dietary calcium on bone calcium utilization

    International Nuclear Information System (INIS)

    Farmer, M.; Roland, D.A. Sr.; Clark, A.J.

    1986-01-01

    In Experiment 1, 10 microCi 45 Ca/day were administered to 125 hens for 10 days. Hens were then allocated to five treatments with calcium levels ranging from .08 to 3.75% of the diet. In Experiment 2, hens with morning oviposition times were randomly allocated to 11 treatments that were periods of time postoviposition ranging from 6 hr to 24 hr, in 2-hr increments (Experiment 2). At the end of each 2-hr period, eggs from 25 hens were removed from the uterus. The 18-, 20-, and 22-hr treatments were replicated three times. In Experiment 3, hens were fed either ad libitum or feed was withheld the last 5 or 6 hr before oviposition. In Experiment 4, hens were fed 10 microCi of 45 Ca for 15 days to label skeletal calcium. Hens were divided into two groups and fed a .08 or 3.75% calcium diet for 2 days. On the second day, 25 hens fed the 3.75% calcium diet were intubated with 7 g of the same diet containing .5 g calcium at 1700, 2100, 0100, 0500, and 0700 hr. The measurements used were egg weight, shell weight, and 45 Ca content of the egg shell. Results indicated a significant linear or quadratic regression of dietary calcium levels on 45 Ca accumulation in eggshells and eggshell weight (Experiment 1). As the calcium level of the diet increased, eggshell weight increased and 45 Ca recovery decreased. Utilization of skeletal calcium for shell formation ranged from 28 to 96%. In Experiment 2, the rate of shell calcification was not constant throughout the calcification process but varied significantly

  19. Calcium Signals from the Vacuole

    Directory of Open Access Journals (Sweden)

    Gerald Schönknecht

    2013-10-01

    Full Text Available The vacuole is by far the largest intracellular Ca2+ store in most plant cells. Here, the current knowledge about the molecular mechanisms of vacuolar Ca2+ release and Ca2+ uptake is summarized, and how different vacuolar Ca2+ channels and Ca2+ pumps may contribute to Ca2+ signaling in plant cells is discussed. To provide a phylogenetic perspective, the distribution of potential vacuolar Ca2+ transporters is compared for different clades of photosynthetic eukaryotes. There are several candidates for vacuolar Ca2+ channels that could elicit cytosolic [Ca2+] transients. Typical second messengers, such as InsP3 and cADPR, seem to trigger vacuolar Ca2+ release, but the molecular mechanism of this Ca2+ release still awaits elucidation. Some vacuolar Ca2+ channels have been identified on a molecular level, the voltage-dependent SV/TPC1 channel, and recently two cyclic-nucleotide-gated cation channels. However, their function in Ca2+ signaling still has to be demonstrated. Ca2+ pumps in addition to establishing long-term Ca2+ homeostasis can shape cytosolic [Ca2+] transients by limiting their amplitude and duration, and may thus affect Ca2+ signaling.

  20. Plasticity of calcium-permeable AMPA glutamate receptors in Pro-opiomelanocortin neurons.

    Science.gov (United States)

    Suyama, Shigetomo; Ralevski, Alexandra; Liu, Zhong-Wu; Dietrich, Marcelo O; Yada, Toshihiko; Simonds, Stephanie E; Cowley, Michael A; Gao, Xiao-Bing; Diano, Sabrina; Horvath, Tamas L

    2017-08-01

    POMC neurons integrate metabolic signals from the periphery. Here, we show in mice that food deprivation induces a linear current-voltage relationship of AMPAR-mediated excitatory postsynaptic currents (EPSCs) in POMC neurons. Inhibition of EPSCs by IEM-1460, an antagonist of calcium-permeable (Cp) AMPARs, diminished EPSC amplitude in the fed but not in the fasted state, suggesting entry of GluR2 subunits into the AMPA receptor complex during food deprivation. Accordingly, removal of extracellular calcium from ACSF decreased the amplitude of mEPSCs in the fed but not the fasted state. Ten days of high-fat diet exposure, which was accompanied by elevated leptin levels and increased POMC neuronal activity, resulted in increased expression of Cp-AMPARs on POMC neurons. Altogether, our results show that entry of calcium via Cp-AMPARs is inherent to activation of POMC neurons, which may underlie a vulnerability of these neurons to calcium overload while activated in a sustained manner during over-nutrition.

  1. Calcium phosphates for biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Canillas, M.; Pena, P.; Aza, A.H. de; Rodriguez, M.A.

    2017-07-01

    The history of calcium phosphates in the medicine field starts in 1769 when the first evidence of its existence in the bone tissue is discovered. Since then, the interest for calcium phosphates has increased among the scientific community. Their study has been developed in parallel with new advances in materials sciences, medicine or tissue engineering areas. Bone tissue engineering is the field where calcium phosphates have had a great importance. While the first bioceramics are selected according to bioinert, biocompatibility and mechanical properties with the aim to replace bone tissue damaged, calcium phosphates open the way to the bone tissue regeneration challenge. Nowadays, they are present in the majority of commercial products directed to repair or regenerate damaged bone tissue. Finally, in the last few decades, they have been suggested and studied as drug delivering devices and as vehicles of DNA and RNA for the future generation therapies. (Author)

  2. [Calcium metabolism after the menopause].

    Science.gov (United States)

    Kanovitch, D; Klotz, H P

    1976-02-16

    The authors recall the antagonism between estradiol and parathormone. Estradiol tends to lower serum calcium and fix calcium in the bones as shown by one of us 25 years ago. The mechanism of this action of estrogen on calcium metabolism has been determined by numerous authors but some points are still not clear, e.g. the interferences between estrogen and calcitonin. Classically, parathormone is known to increase bony reabsorption and raise serum calcium. After the menopause the gradual reduction in estradiol secretion leads to post-menopausal osteoporosis. It is better to administer estrogens prophylactically to women after the menopause provided a cervical smear and mammography have been carried out to eliminate latent carcinoma of the breast or uterine cervix.

  3. Calcium phosphates for biomedical applications

    Directory of Open Access Journals (Sweden)

    Maria Canillas

    2017-05-01

    Full Text Available The history of calcium phosphates in the medicine field starts in 1769 when the first evidence of its existence in the bone tissue is discovered. Since then, the interest for calcium phosphates has increased among the scientific community. Their study has been developed in parallel with new advances in materials sciences, medicine or tissue engineering areas. Bone tissue engineering is the field where calcium phosphates have had a great importance. While the first bioceramics are selected according to bioinert, biocompatibility and mechanical properties with the aim to replace bone tissue damaged, calcium phosphates open the way to the bone tissue regeneration challenge. Nowadays, they are present in the majority of commercial products directed to repair or regenerate damaged bone tissue. Finally, in the last few decades, they have been suggested and studied as drug delivering devices and as vehicles of DNA and RNA for the future generation therapies.

  4. Calcium-sensing beyond neurotransmitters

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Han, Weiping

    2009-01-01

    Neurotransmitters, neuropeptides and hormones are released through the regulated exocytosis of SVs (synaptic vesicles) and LDCVs (large dense-core vesicles), a process that is controlled by calcium. Synaptotagmins are a family of type 1 membrane proteins that share a common domain structure. Most....... Also, we discuss potential roles of synaptotagmins in non-traditional endocrine systems....... synaptotagmins are located in brain and endocrine cells, and some of these synaptotagmins bind to phospholipids and calcium at levels that trigger regulated exocytosis of SVs and LDCVs. This led to the proposed synaptotagmin-calcium-sensor paradigm, that is, members of the synaptotagmin family function...... as calcium sensors for the regulated exocytosis of neurotransmitters, neuropeptides and hormones. Here, we provide an overview of the synaptotagmin family, and review the recent mouse genetic studies aimed at understanding the functions of synaptotagmins in neurotransmission and endocrine-hormone secretion...

  5. Fortification of milk with calcium: effect on calcium bioavailability and interactions with iron and zinc.

    Science.gov (United States)

    Perales, Sara; Barberá, Reyes; Lagarda, María Jesús; Farré, Rosaura

    2006-06-28

    Calcium solubility, dialysability, and transport and uptake (retention + transport) by Caco-2 cells as indicators of calcium bioavailability have been estimated in the in vitro gastrointestinal digests of milk and calcium fortified milk. A significant linear correlation (p calcium uptake and the amount of soluble calcium added to the cells, and also between percentage calcium uptake and the calcium measured in the analyzed samples. The solubility, dialysis, transport, and uptake values are higher (p calcium fortified milks than for nonfortified milks; that is, calcium fortification increases not only calcium content but also its bioavailability. An inhibitory effect of calcium from fortified milks upon iron absorption was found. The observed effect of calcium from fortified milks upon zinc bioavailability depends on the in vitro method used, zinc solubility and dialysis decrease in calcium fortified milks, and percentage zinc uptake remains unchanged.

  6. Calcium metabolism and cardiovascular function after spaceflight

    Science.gov (United States)

    Hatton, Daniel C.; Yue, Qi; Dierickx, Jacqueline; Roullet, Chantal; Otsuka, Keiichi; Watanabe, Mitsuaki; Coste, Sarah; Roullet, Jean Baptiste; Phanouvang, Thongchan; Orwoll, Eric; hide

    2002-01-01

    To determine the influence of dietary calcium on spaceflight-induced alterations in calcium metabolism and blood pressure (BP), 9-wk-old spontaneously hypertensive rats, fed either high- (2%) or low-calcium (0.02%) diets, were flown on an 18-day shuttle flight. On landing, flight animals had increased ionized calcium (P Basal and thrombin-stimulated platelet free calcium (intracellular calcium concentration) were also reduced (P metabolism (P metabolism are relatively impervious to dietary calcium in the short term, 2) increased ionized calcium did not normalize low-calcium-induced elevations of BP, and 3) parathyroid hormone was paradoxically increased in the high-calcium-fed flight animals after landing.

  7. Calcium affects on vascular endpoints

    Directory of Open Access Journals (Sweden)

    Patel Vaishali B

    2012-03-01

    Full Text Available Abstract Calcium is one of the most abundant minerals in the body and its metabolism is one of the basic biologic processes in humans. Although historically linked primarily to bone structural development and maintenance, calcium is now recognized as a key component of many physiologic pathways necessary for optimum health including cardiovascular, neurological, endocrine, renal, and gastrointestinal systems. A recent meta-analysis published in August 2011 showed a potential increase in cardiovascular events related to calcium supplementation. The possible mechanism of action of this correlation has not been well elucidated. This topic has generated intense interest due to the widespread use of calcium supplements, particularly among the middle aged and elderly who are at the most risk from cardiac events. Prior studies did not control for potential confounding factors such as the use of statins, aspirin or other medications. These controversial results warrant additional well-designed studies to investigate the relationship between calcium supplementation and cardiovascular outcomes. The purpose of this review is to highlight the current literature in regards to calcium supplementation and cardiovascular health; and to identify areas of future research.

  8. Does insulin resistance, visceral adiposity, or a sex hormone alteration underlie the metabolic syndrome? Studies in women.

    Science.gov (United States)

    Phillips, Gerald B; Jing, Tianyi; Heymsfield, Steven B

    2008-06-01

    Insulin resistance, obesity, and a sex hormone alteration have each been suggested as the underlying link for the constellation of risk factors for myocardial infarction (MI) commonly referred to as the metabolic syndrome or the insulin resistance syndrome. In an attempt to identify in women which of these variables is the most likely link, insulin, adiposity variables, sex hormones, and risk factors for MI were measured and their relationships analyzed statistically in 58 premenopausal and 20 postmenopausal healthy women. On controlling for age, visceral adipose tissue (VAT) correlated more strongly with risk factors for MI, insulin, and free testosterone (FT) than did total adipose tissue or subcutaneous adipose tissue. VAT, therefore, was used as the adiposity variable for further data analysis. Waist circumference was a better surrogate of VAT than was waist-hip ratio, which was a poor surrogate of VAT. VAT correlated positively with insulin, FT, triglyceride, and glucose, and negatively with high-density lipoprotein and sex hormone-binding globulin. On controlling for age, FT and insulin correlated with risk factors for MI and with each other, but on controlling for age and VAT, all of their correlations lost statistical significance except for FT-triglyceride and FT-insulin in the postmenopausal women. In conclusion, VAT accumulation in women, independently of other measures of adiposity, may largely explain the correlations of insulin, obesity, and sex hormones with risk factors for MI and may be the immediate underlying factor that links risk factors for MI to form the metabolic syndrome. Insulin resistance, which has been generally accepted to be the underlying factor, may be a component of the syndrome rather than its underlying link. We hypothesize that in women FT may effect preferential VAT accumulation and induce insulin resistance directly, as well as via VAT accumulation, so that a sex hormone alteration may underlie VAT accumulation and thus

  9. Modeling Calcium Microdomains using Homogenisation

    Science.gov (United States)

    Higgins, Erin R.; Goel, Pranay; Puglisi, Jose L.; Bers, Donald M.; Cannell, Mark; Sneyd, James

    2007-01-01

    Microdomains of calcium (i.e., areas on the nanometer scale that have qualitatively different calcium concentrations from that in the bulk cytosol) are known to be important in many situations. In cardiac cells, for instance, a calcium microdomain between the L-type channels and the ryanodine receptors, the so-called diadic cleft, is where the majority of the control of calcium release occurs. In other cell types that exhibit calcium oscillations and waves, the importance of microdomains in the vicinity of clusters of inositol trisphosphate receptors, or between the endoplasmic reticulum (ER) and other internal organelles or the plasma membrane, is clear. Given the limits of computational power, it is not currently realistic to model an entire cellular cytoplasm by incorporating detailed structural information about the ER throughout the entire cytoplasm. Hence, most models use a homogenised approach, assuming that both cytoplasm and ER coexist at each point of the domain. Conversely, microdomain models can be constructed, in which detailed structural information can be incorporated, but, until now, methods have not been developed for linking such a microdomain model to a model at the level of the entire cell. Using the homogenisation approach we developed in an earlier paper (Goel P., A. Friedman and J. Sneyd. 2006. Homogenization of the cell cytoplasm: the calcium bidomain equations. SIAM J. on Multiscale Modeling and Simulation, in press) we show how a multiscale model of a calcium microdomain can be constructed. In this model a detailed model of the microdomain (in which the ER and the cytoplasm are separate compartments) is coupled to a homogenised model of the entire cell in a rigorous way. Our method is illustrated by a simple model of the diadic cleft of a cardiac half-sarcomere. PMID:17499276

  10. Calcium: the molecular basis of calcium action in biology and medicine

    National Research Council Canada - National Science Library

    Pochet, Roland; Donato, Rosario

    2000-01-01

    ... of Calcium Calcium Signalling in Excitable Cells Ca2+ Release in Muscle Cells by N. Macrez and J. Mironneau Calcium Signalling in Neurons Exemplified by Rat Sympathetic Ganglion Cells by S.J. M...

  11. Lead in calcium supplements (abstract)

    International Nuclear Information System (INIS)

    Rehman, S.; Khalid, N.

    2011-01-01

    Lead present in calcium supplements is of grave concern as some lead levels have been measured up to the extent of regulatory limit set by the United States. Calcium supplements inevitably get contaminated with lead as both are naturally occurring elements. Therefore, it is imperative to indicate its level in these supplements in order to create awareness among consumers. In this study, a sophisticated analytical technique, atomic absorption spectrometry was used to analyze Pb contents in 27 commonly consumed Ca supplements manufactured by different national and multinational companies. The daily intake of lead through these supplements was calculated. Only 10% of the calcium supplements analyzed met the criteria of acceptable Pb levels (1.5 mu g/daily dose) in supplements/consumer products set by the United States. It was also found that Pb intake was highest in chelated calcium supplements 28.5 mu g/daily dose, whereas lowest 0.47 mu g/daily dose through calcium supplements with vitamin D formulation. In order to validate our results from the study conducted, IAEA-certified reference material (animal bone, H-5) was analyzed for its Pb levels. The levels of Pb determined were quite in good agreement with the certified values. (author)

  12. Calcium metabolism and cardiovascular function after spaceflight

    Science.gov (United States)

    Hatton, Daniel C.; Yue, Qi; Dierickx, Jacqueline; Roullet, Chantal; Otsuka, Keiichi; Watanabe, Mitsuaki; Coste, Sarah; Roullet, Jean Baptiste; Phanouvang, Thongchan; Orwoll, Eric; hide

    2002-01-01

    To determine the influence of dietary calcium on spaceflight-induced alterations in calcium metabolism and blood pressure (BP), 9-wk-old spontaneously hypertensive rats, fed either high- (2%) or low-calcium (0.02%) diets, were flown on an 18-day shuttle flight. On landing, flight animals had increased ionized calcium (P parathyroid hormone levels (P animals (P = 0.057). However, mean arterial pressure was elevated (P animals fed low- compared with high-calcium diets (P parathyroid hormone was paradoxically increased in the high-calcium-fed flight animals after landing.

  13. Calcium signaling and cell proliferation.

    Science.gov (United States)

    Pinto, Mauro Cunha Xavier; Kihara, Alexandre Hiroaki; Goulart, Vânia A M; Tonelli, Fernanda M P; Gomes, Katia N; Ulrich, Henning; Resende, Rodrigo R

    2015-11-01

    Cell proliferation is orchestrated through diverse proteins related to calcium (Ca(2+)) signaling inside the cell. Cellular Ca(2+) influx that occurs first by various mechanisms at the plasma membrane, is then followed by absorption of Ca(2+) ions by mitochondria and endoplasmic reticulum, and, finally, there is a connection of calcium stores to the nucleus. Experimental evidence indicates that the fluctuation of Ca(2+) from the endoplasmic reticulum provides a pivotal and physiological role for cell proliferation. Ca(2+) depletion in the endoplasmatic reticulum triggers Ca(2+) influx across the plasma membrane in an phenomenon called store-operated calcium entries (SOCEs). SOCE is activated through a complex interplay between a Ca(2+) sensor, denominated STIM, localized in the endoplasmic reticulum and a Ca(2+) channel at the cell membrane, denominated Orai. The interplay between STIM and Orai proteins with cell membrane receptors and their role in cell proliferation is discussed in this review. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. The effect of variable calcium and very low calcium diets on human calcium metabolism. Ph.D. Thesis. Final Report

    Science.gov (United States)

    Chu, J.

    1971-01-01

    The effects of a very low calcium diet, with variable high and low protein intake, on the dynamics of calcium metabolism and the mechanism of calciuretics, are examined. The experiment, using male subjects, was designed to study the role of intestinal calcium absorption on urinary calcium excretion, and the rate of production of endogeneously secreted calcium in the gastrointestinal tract. The study showed an average of 70% fractional absorption rate during very low calcium intake, and that a decrease in renal tubular reabsorption of calcium is responsible for calciuretic effects of high protein intake. The study also indicates that there is a tendency to develop osteoporosis after long periods of low calcium intake, especially with a concurrent high protein intake.

  15. Leveraging the coronary calcium scan beyond the coronary calcium score

    NARCIS (Netherlands)

    D. Bos (Daniel); M.J.G. Leening (Maarten)

    2018-01-01

    textabstractAbstract: Non-contrast cardiac computed tomography in order to obtain the coronary artery calcium score has become an established diagnostic procedure in the clinical setting, and is commonly employed in clinical and population-based research. This state-of-the-art review paper

  16. Calcium fortification of breakfast cereal enhances calcium absorption in children without affecting iron absorption.

    Science.gov (United States)

    Abrams, S A; Griffin, I J; Davila, P; Liang, L

    2001-10-01

    Provision of calcium-fortified foods may represent an important component of improving the calcium intake of children. We sought to determine whether the addition of calcium to cereal would have a net positive effect on calcium absorption without decreasing iron absorption. Twenty-seven children, 6 to 9 years of age, were provided two servings per day (30 g of cereal per serving) of either a low (39 mg/serving) or fortified (156 mg/serving) calcium-containing cereal product for 14 days. Calcium absorption was measured by using stable isotopes added to milk (extrinsically labeled) and to the calcium-fortified cereal (intrinsically labeled). Fractional calcium absorption from the fortified cereal was virtually identical to that from milk. Fractional absorption of calcium from milk did not differ significantly when given with enriched or low-calcium-containing cereal. Total calcium absorption increased from 215 +/- 45 mg/d to 269 +/- 45 mg/d with the addition of the calcium-fortified cereal (P Iron absorption was similar when children received the calcium-fortified cereal or unfortified cereal. The addition of a moderate amount of calcium to a cereal product was beneficial to calcium absorption and did not interfere with iron absorption. Use of calcium-fortified food products may be considered a practical approach to increasing the calcium intake of children.

  17. Vitamin D and intestinal calcium absorption.

    Science.gov (United States)

    Christakos, Sylvia; Dhawan, Puneet; Porta, Angela; Mady, Leila J; Seth, Tanya

    2011-12-05

    The principal function of vitamin D in calcium homeostasis is to increase calcium absorption from the intestine. Calcium is absorbed by both an active transcellular pathway, which is energy dependent, and by a passive paracellular pathway through tight junctions. 1,25Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) the hormonally active form of vitamin D, through its genomic actions, is the major stimulator of active intestinal calcium absorption which involves calcium influx, translocation of calcium through the interior of the enterocyte and basolateral extrusion of calcium by the intestinal plasma membrane pump. This article reviews recent studies that have challenged the traditional model of vitamin D mediated transcellular calcium absorption and the crucial role of specific calcium transport proteins in intestinal calcium absorption. There is also increasing evidence that 1,25(OH)(2)D(3) can enhance paracellular calcium diffusion. The influence of estrogen, prolactin, glucocorticoids and aging on intestinal calcium absorption and the role of the distal intestine in vitamin D mediated intestinal calcium absorption are also discussed. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  18. Natural Variation in SER1 and ENA6 Underlie Condition-Specific Growth Defects in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Amy Sirr

    2018-01-01

    Full Text Available Despite their ubiquitous use in laboratory strains, naturally occurring loss-of-function mutations in genes encoding core metabolic enzymes are relatively rare in wild isolates of Saccharomyces cerevisiae. Here, we identify a naturally occurring serine auxotrophy in a sake brewing strain from Japan. Through a cross with a honey wine (white tecc brewing strain from Ethiopia, we map the minimal medium growth defect to SER1, which encodes 3-phosphoserine aminotransferase and is orthologous to the human disease gene, PSAT1. To investigate the impact of this polymorphism under conditions of abundant external nutrients, we examine growth in rich medium alone or with additional stresses, including the drugs caffeine and rapamycin and relatively high concentrations of copper, salt, and ethanol. Consistent with studies that found widespread effects of different auxotrophies on RNA expression patterns in rich media, we find that the SER1 loss-of-function allele dominates the quantitative trait locus (QTL landscape under many of these conditions, with a notable exacerbation of the effect in the presence of rapamycin and caffeine. We also identify a major-effect QTL associated with growth on salt that maps to the gene encoding the sodium exporter, ENA6. We demonstrate that the salt phenotype is largely driven by variation in the ENA6 promoter, which harbors a deletion that removes binding sites for the Mig1 and Nrg1 transcriptional repressors. Thus, our results identify natural variation associated with both coding and regulatory regions of the genome that underlie strong growth phenotypes.

  19. Calcium fertilization increases the concentration of calcium in sapwood and calcium oxalate in foliage of red spruce

    Science.gov (United States)

    Kevin T. Smith; Walter C. Shortle; Jon H. Connolly; Rakesh Minocha; Jody Jellison

    2009-01-01

    Calcium cycling plays a key role in the health and productivity of red spruce forests in the northeastern US. A portion of the flowpath of calcium within forests includes translocation as Ca2+ in sapwood and accumulation as crystals of calcium oxalate in foliage. Concentrations of Ca in these tree tissues have been used as markers of...

  20. Extra-intestinal calcium handling contributes to normal serum calcium levels when intestinal calcium absorption is suboptimal.

    Science.gov (United States)

    Lieben, Liesbet; Verlinden, Lieve; Masuyama, Ritsuko; Torrekens, Sophie; Moermans, Karen; Schoonjans, Luc; Carmeliet, Peter; Carmeliet, Geert

    2015-12-01

    The active form of vitamin D, 1,25(OH)2D, is a crucial regulator of calcium homeostasis, especially through stimulation of intestinal calcium transport. Lack of intestinal vitamin D receptor (VDR) signaling does however not result in hypocalcemia, because the increased 1,25(OH)2D levels stimulate calcium handling in extra-intestinal tissues. Systemic VDR deficiency, on the other hand, results in hypocalcemia because calcium handling is impaired not only in the intestine, but also in kidney and bone. It remains however unclear whether low intestinal VDR activity, as observed during aging, is sufficient for intestinal calcium transport and for mineral and bone homeostasis. To this end, we generated mice that expressed the Vdr exclusively in the gut, but at reduced levels. We found that ~15% of intestinal VDR expression greatly prevented the Vdr null phenotype in young-adult mice, including the severe hypocalcemia. Serum calcium levels were, however, in the low-normal range, which may be due to the suboptimal intestinal calcium absorption, renal calcium loss, insufficient increase in bone resorption and normal calcium incorporation in the bone matrix. In conclusion, our results indicate that low intestinal VDR levels improve intestinal calcium absorption compared to Vdr null mice, but also show that 1,25(OH)2D-mediated fine-tuning of renal calcium reabsorption and bone mineralization and resorption is required to maintain fully normal serum calcium levels. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Estimation of presynaptic calcium currents and endogenous calcium buffers at the frog neuromuscular junction with two different calcium fluorescent dyes

    Directory of Open Access Journals (Sweden)

    Dmitry eSamigullin

    2015-01-01

    Full Text Available At the frog neuromuscular junction, under physiological conditions, the direct measurement of calcium currents and of the concentration of intracellular calcium buffers—which determine the kinetics of calcium concentration and neurotransmitter release from the nerve terminal—has hitherto been technically impossible. With the aim of quantifying both Ca2+ currents and the intracellular calcium buffers, we measured fluorescence signals from nerve terminals loaded with the low-affinity calcium dye Magnesium Green or the high-affinity dye Oregon Green BAPTA-1, simultaneously with microelectrode recordings of nerve-action potentials and end-plate currents. The action-potential-induced fluorescence signals in the nerve terminals developed much more slowly than the postsynaptic response. To clarify the reasons for this observation and to define a spatiotemporal profile of intracellular calcium and of the concentration of mobile and fixed calcium buffers, mathematical modeling was employed. The best approximations of the experimental calcium transients for both calcium dyes were obtained when the calcium current had an amplitude of 1.6 ± 0.08 рА and a half-decay time of 1.2 ± 0.06 ms, and when the concentrations of mobile and fixed calcium buffers were 250 ± 13 µM and 8 ± 0.4 mM, respectively. High concentrations of endogenous buffers define the time course of calcium transients after an action potential in the axoplasm, and may modify synaptic plasticity.

  2. Estimation of presynaptic calcium currents and endogenous calcium buffers at the frog neuromuscular junction with two different calcium fluorescent dyes.

    Science.gov (United States)

    Samigullin, Dmitry; Fatikhov, Nijaz; Khaziev, Eduard; Skorinkin, Andrey; Nikolsky, Eugeny; Bukharaeva, Ellya

    2014-01-01

    At the frog neuromuscular junction, under physiological conditions, the direct measurement of calcium currents and of the concentration of intracellular calcium buffers-which determine the kinetics of calcium concentration and neurotransmitter release from the nerve terminal-has hitherto been technically impossible. With the aim of quantifying both Ca(2+) currents and the intracellular calcium buffers, we measured fluorescence signals from nerve terminals loaded with the low-affinity calcium dye Magnesium Green or the high-affinity dye Oregon Green BAPTA-1, simultaneously with microelectrode recordings of nerve-action potentials and end-plate currents. The action-potential-induced fluorescence signals in the nerve terminals developed much more slowly than the postsynaptic response. To clarify the reasons for this observation and to define a spatiotemporal profile of intracellular calcium and of the concentration of mobile and fixed calcium buffers, mathematical modeling was employed. The best approximations of the experimental calcium transients for both calcium dyes were obtained when the calcium current had an amplitude of 1.6 ± 0.08 pA and a half-decay time of 1.2 ± 0.06 ms, and when the concentrations of mobile and fixed calcium buffers were 250 ± 13 μM and 8 ± 0.4 mM, respectively. High concentrations of endogenous buffers define the time course of calcium transients after an action potential in the axoplasm, and may modify synaptic plasticity.

  3. Vitamin D, Calcium, and Bone Health

    Science.gov (United States)

    ... Bone Health Featured Resource Find an Endocrinologist Search Vitamin D, Calcium, and Bone Health Download PDFs English Espanol ... also helps keep your bones strong. Why are vitamin D and calcium important to bone health? Vitamin D ...

  4. Dairy Dilemma: Are You Getting Enough Calcium?

    Science.gov (United States)

    ... to grow and stay strong. The body also needs vitamin D to absorb calcium. Nutrition surveys have shown ... found in dairy products. How much calcium and vitamin D you need depends on your age and other factors. If ...

  5. 21 CFR 182.8217 - Calcium phosphate.

    Science.gov (United States)

    2010-04-01

    ... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8217 Calcium phosphate. (a) Product. Calcium phosphate (mono-, di-, and tribasic). (b) Conditions of use. This substance...

  6. 21 CFR 182.8223 - Calcium pyrophosphate.

    Science.gov (United States)

    2010-04-01

    ... FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use. This substance is generally recognized...

  7. Familial hypocalciuric hypercalcemia and calcium sensing receptor

    DEFF Research Database (Denmark)

    Mrgan, Monija; Nielsen, Sanne; Brixen, Kim

    2014-01-01

    Familial hypocalciuric hypercalcemia (FHH) is a lifelong, benign autosomal dominant disease characterized by hypercalcemia, normal to increased parathyroid hormone level, and a relatively low renal calcium excretion. Inactivation of the calcium-sensing receptor in heterozygous patients results in...

  8. Does Growth in the Executive System of Working Memory Underlie Growth in Literacy for Bilingual Children with and without Reading Disabilities?

    Science.gov (United States)

    Swanson, H. Lee; Orosco, Michael J.; Kudo, Milagros

    2017-01-01

    This cohort-sequential study explored the components of working memory (WM) that underlie second language (L2) reading growth in 450 children at risk and not at risk for reading disabilities (RD) whose first language is Spanish. English language learners designated as balanced and nonbalanced bilinguals with and without risk for RD in Grades 1, 2,…

  9. Anoctamin Calcium-Activated Chloride Channels May Modulate Inhibitory Transmission in the Cerebellar Cortex.

    Directory of Open Access Journals (Sweden)

    Weiping Zhang

    Full Text Available Calcium-activated chloride channels of the anoctamin (alias TMEM16 protein family fulfill critical functions in epithelial fluid transport, smooth muscle contraction and sensory signal processing. Little is known, however, about their contribution to information processing in the central nervous system. Here we examined the recent finding that a calcium-dependent chloride conductance impacts on GABAergic synaptic inhibition in Purkinje cells of the cerebellum. We asked whether anoctamin channels may underlie this chloride conductance. We identified two anoctamin channel proteins, ANO1 and ANO2, in the cerebellar cortex. ANO1 was expressed in inhibitory interneurons of the molecular layer and the granule cell layer. Both channels were expressed in Purkinje cells but, while ANO1 appeared to be retained in the cell body, ANO2 was targeted to the dendritic tree. Functional studies confirmed that ANO2 was involved in a calcium-dependent mode of ionic plasticity that reduces the efficacy of GABAergic synapses. ANO2 channels attenuated GABAergic transmission by increasing the postsynaptic chloride concentration, hence reducing the driving force for chloride influx. Our data suggest that ANO2 channels are involved in a Ca2+-dependent regulation of synaptic weight in GABAergic inhibition. Thus, in balance with the chloride extrusion mechanism via the co-transporter KCC2, ANO2 appears to regulate ionic plasticity in the cerebellum.

  10. Calcium-tolerant anionic surfactants

    NARCIS (Netherlands)

    Kooreman, Alexander

    1995-01-01

    One of the problems of applying anionic surfactants in, for example, laundry detergents is the precipitation of calcium salts. Much effort has been directed towards avoiding precipitation. There are at least three ways for tackling the problem. The first involves the use of a large quantity of

  11. Calcium – how and why?

    Indian Academy of Sciences (India)

    Unknown

    muscle cells, he demonstrated that it was only calcium that could cause the muscle fibre to contract (Heilbrunn and Wiercinski 1947). Later in 1952, Sandow proposed the term excitation-contraction coupling for this phe- nomenon. Heilbrunn's views are best summarized by the following statement published in 1937 in his ...

  12. Discovery and Development of Calcium Channel Blockers

    OpenAIRE

    Godfraind, Théophile

    2017-01-01

    In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovere...

  13. Absorbability of calcium from calcium-bound phosphoryl oligosaccharides in comparison with that from various calcium compounds in the rat ligated jejunum loop.

    Science.gov (United States)

    To-o, Kenji; Kamasaka, Hiroshi; Nishimura, Takahisa; Kuriki, Takashi; Saeki, Shigeru; Nakabou, Yukihiro

    2003-08-01

    Calcium-bound phosphoryl oligosaccharides (POs-Ca) were prepared from potato starch. Their solubility and in situ absorbability as a calcium source were investigated by comparing with the soluble calcium compounds, calcium chloride and calcium lactate, or insoluble calcium compounds, calcium carbonate and dibasic calcium phosphate. The solubility of POs-Ca was as high as that of calcium chloride and about 3-fold higher than that of calcium lactate. An in situ experiment showed that the intestinal calcium absorption rate of POs-Ca was almost comparable with that of the soluble calcium compounds, and was significantly higher (pcalcium groups. Moreover, the total absorption rate of a 1:1 mixture of the calcium from POs-Ca and a whey mineral complex (WMC) was significantly higher (psoluble calcium source with relatively high absorption in the intestinal tract.

  14. Mechanism of store-operated calcium entry

    Indian Academy of Sciences (India)

    Activation of receptors coupled to the phospholipase C/IP3 signalling pathway results in a rapid release of calcium from its intracellular stores, eventually leading to depletion of these stores. Calcium store depletion triggers an influx of extracellular calcium across the plasma membrane, a mechanism known as the ...

  15. Physicochemical characterization of zinc-substituted calcium ...

    Indian Academy of Sciences (India)

    to form synthetic calcium phosphates incorporated with. Zn, such as zinc acetate and calcium acetate, 65% nitric acid, sodium hydrogen phosphate, trietanoloamine, 0.025 M. EDTA, calcein indicator and 35–38% hydrochloric acid were purchased from POCh SA. Other reagents necessary for determining amount of calcium, ...

  16. 21 CFR 582.5217 - Calcium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium phosphate. 582.5217 Section 582.5217 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5217 Calcium phosphate. (a) Product. Calcium phosphate (mono-, di-, and tribasic). (b...

  17. 21 CFR 582.1217 - Calcium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium phosphate. 582.1217 Section 582.1217 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1217 Calcium phosphate. (a) Product. Calcium phosphate (mono-, di-, and tribasic). (b...

  18. Modularized study of human calcium signalling pathway

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    The idea is used here to break human calcium signalling pathway into simple entities known as ... [Nayak L and De R K 2007 Modularized study of human calcium signalling pathway; J. Biosci. 32 1009–1017] http://www.ias.ac.in/ ..... cellular physiology of intracellular calcium stores; Physiol. Rev. 74 595–636. Bertram R ...

  19. Effect of purines on calcium-independent acetylcholine release at the mouse neuromuscular junction.

    Science.gov (United States)

    Veggetti, M; Muchnik, S; Losavio, A

    2008-07-17

    At the mouse neuromuscular junction, activation of adenosine A(1) and P2Y receptors inhibits acetylcholine release by an effect on voltage dependent calcium channels related to spontaneous and evoked secretion. However, an effect of purines upon the neurotransmitter-releasing machinery downstream of Ca(2+) influx cannot be ruled out. An excellent tool to study neurotransmitter exocytosis in a Ca(2+)-independent step is the hypertonic response. Intracellular recordings were performed on diaphragm fibers of CF1 mice to determine the action of the specific adenosine A(1) receptor agonist 2-chloro-N(6)-cyclopentyl-adenosine (CCPA) and the P2Y(12-13) agonist 2-methylthio-adenosine 5'-diphosphate (2-MeSADP) on the hypertonic response. Both purines significantly decreased such response (peak and area under the curve), and their effect was prevented by specific antagonists of A(1) and P2Y(12-13) receptors, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and N-[2-(methylthioethyl)]-2-[3,3,3-trifluoropropyl]thio-5'-adenylic acid, monoanhydride with dichloromethylenebiphosphonic acid, tetrasodium salt (AR-C69931MX), respectively. Moreover, incubation of preparations only with the antagonists induced a higher response compared with controls, suggesting that endogenous ATP/ADP and adenosine are able to modulate the hypertonic response by activating their specific receptors. To search for the intracellular pathways involved in this effect, we studied the action of CCPA and 2-MeSADP in hypertonicity in the presence of inhibitors of several pathways. We found that the effect of CPPA was prevented by the calmodulin antagonist N-(6-aminohexil)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) while that of 2-MeSADP was occluded by the protein kinase C antagonist chelerythrine and W-7. On the other hand, the inhibitors of protein kinase A (N-(2[pbromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide, H-89) and phosphoinositide-3 kinase (PI3K) (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran

  20. Calcium Orthophosphate-Based Bioceramics

    Directory of Open Access Journals (Sweden)

    Sergey V. Dorozhkin

    2013-09-01

    Full Text Available Various types of grafts have been traditionally used to restore damaged bones. In the late 1960s, a strong interest was raised in studying ceramics as potential bone grafts due to their biomechanical properties. A bit later, such synthetic biomaterials were called bioceramics. In principle, bioceramics can be prepared from diverse materials but this review is limited to calcium orthophosphate-based formulations only, which possess the specific advantages due to the chemical similarity to mammalian bones and teeth. During the past 40 years, there have been a number of important achievements in this field. Namely, after the initial development of bioceramics that was just tolerated in the physiological environment, an emphasis was shifted towards the formulations able to form direct chemical bonds with the adjacent bones. Afterwards, by the structural and compositional controls, it became possible to choose whether the calcium orthophosphate-based implants remain biologically stable once incorporated into the skeletal structure or whether they were resorbed over time. At the turn of the millennium, a new concept of regenerative bioceramics was developed and such formulations became an integrated part of the tissue engineering approach. Now calcium orthophosphate scaffolds are designed to induce bone formation and vascularization. These scaffolds are often porous and harbor different biomolecules and/or cells. Therefore, current biomedical applications of calcium orthophosphate bioceramics include bone augmentations, artificial bone grafts, maxillofacial reconstruction, spinal fusion, periodontal disease repairs and bone fillers after tumor surgery. Perspective future applications comprise drug delivery and tissue engineering purposes because calcium orthophosphates appear to be promising carriers of growth factors, bioactive peptides and various types of cells.

  1. Commitment of Satellite Cells Expressing the Calcium Channel α2δ1 Subunit to the Muscle Lineage

    Science.gov (United States)

    Tamayo, Tammy; Grajales, Liliana; García, Jesús

    2012-01-01

    Satellite cells can maintain or repair muscle because they possess stem cell properties, making them a valuable option for cell therapy. However, cell transplants into skeletal muscle of patients with muscular dystrophy are limited by donor cell attachment, migration, and survival in the host tissue. Cells used for therapy are selected based on specific markers present in the plasma membrane. Although many markers have been identified, there is a need to find a marker that is expressed at different states in satellite cells, activated, quiescent, or differentiated cell. Furthermore, the marker has to be present in human tissue. Recently we reported that the plasma membrane α2δ1 protein is involved in cell attachment and migration in myoblasts. The α2δ1 subunit forms a part of the L-type voltage-dependent calcium channel in adult skeletal muscle. We found that the α2δ1 subunit is expressed in the majority of newly isolated satellite cells and that it appears earlier than the α1 subunits and at higher levels than the β or γ subunits. We also found that those cells that expressed α2δ1 would differentiate into muscle cells. This evidence indicates that the α2δ1 may be used as a marker of satellite cells that will differentiate into muscle. PMID:23251796

  2. Characterisation of marrubenol, a diterpene extracted from Marrubium vulgare, as an L-type calcium channel blocker.

    Science.gov (United States)

    El-Bardai, Sanae; Wibo, Maurice; Hamaide, Marie-Christine; Lyoussi, Badiaa; Quetin-Leclercq, Joelle; Morel, Nicole

    2003-12-01

    1. The objective of the present study was to investigate the mechanism of the relaxant activity of marrubenol, a diterpenoid extracted from Marrubium vulgare. In rat aorta, marrubenol was a more potent inhibitor of the contraction evoked by 100 mM KCl (IC50: 11.8+/-0.3 microM, maximum relaxation: 93+/-0.6%) than of the contraction evoked by noradrenaline (maximum relaxation: 30+/-1.5%). 2. In fura-2-loaded aorta, marrubenol simultaneously inhibited the Ca2+ signal and the contraction evoked by 100 mM KCl, and decreased the quenching rate of fura-2 fluorescence by Mn2+. 3. Patch-clamp data obtained in aortic smooth muscle cells (A7r5) indicated that marrubenol inhibited Ba2+ inward current in a voltage-dependent manner (KD: 8+/-2 and 40+/-6 microM at holding potentials of -50 and -100 mV, respectively). 4. These results showed that marrubenol inhibits smooth muscle contraction by blocking L-type calcium channels.

  3. Commitment of Satellite Cells Expressing the Calcium Channel α2δ1 Subunit to the Muscle Lineage

    Directory of Open Access Journals (Sweden)

    Tammy Tamayo

    2012-01-01

    Full Text Available Satellite cells can maintain or repair muscle because they possess stem cell properties, making them a valuable option for cell therapy. However, cell transplants into skeletal muscle of patients with muscular dystrophy are limited by donor cell attachment, migration, and survival in the host tissue. Cells used for therapy are selected based on specific markers present in the plasma membrane. Although many markers have been identified, there is a need to find a marker that is expressed at different states in satellite cells, activated, quiescent, or differentiated cell. Furthermore, the marker has to be present in human tissue. Recently we reported that the plasma membrane α2δ1 protein is involved in cell attachment and migration in myoblasts. The α2δ1 subunit forms a part of the L-type voltage-dependent calcium channel in adult skeletal muscle. We found that the α2δ1 subunit is expressed in the majority of newly isolated satellite cells and that it appears earlier than the α1 subunits and at higher levels than the β or γ subunits. We also found that those cells that expressed α2δ1 would differentiate into muscle cells. This evidence indicates that the α2δ1 may be used as a marker of satellite cells that will differentiate into muscle.

  4. Abnormal frontal theta oscillations underlie the cognitive flexibility deficits in children with high-functioning autism spectrum disorders.

    Science.gov (United States)

    Yeung, Michael K; Han, Yvonne M Y; Sze, Sophia L; Chan, Agnes S

    2016-03-01

    Deficits in cognitive flexibility have been suggested to underlie the repetitive and stereotyped behavior in individuals with autism spectrum disorders (ASD). Because cognitive flexibility is primarily mediated by the frontal lobe, where structural and functional abnormalities have been extensively found in these individuals, it is conceivable that their deficits in cognitive flexibility are related to abnormal activations of the frontal lobe. The present study investigates cognitive flexibility and its underlying neurophysiological activities as indicated by theta oscillations in children with ASD. Twenty-five children with high-functioning ASD and 25 IQ- and age-matched typically developing (TD) children were subjected to neuropsychological assessments on cognitive flexibility and electroencephalography recordings. The children with ASD performed significantly worse than the TD children across the tasks of cognitive flexibility, including the modified Wisconsin Card Sorting Test (WCST). These children also demonstrated a reduced increase of the theta power localized in multiple brain regions, including various sectors of the frontal lobe at the late stage (i.e., 600 ms-900 ms poststimulus interval) but not the early stage (i.e., 250 ms-550 ms poststimulus interval) of the performance of the modified WCST. The suppressed late frontal theta activities were further shown to be significantly correlated with a poorer performance on the cognitive flexibility measures. Our findings suggest that abnormal activations of multiple cortical regions, especially the frontal lobe, form the neural basis of the cognitive flexibility deficits in children with ASD. In addition, we found an EEG marker of cognitive flexibility which could be used to monitor treatment outcomes objectively. (c) 2016 APA, all rights reserved).

  5. Computational study of a calcium release-activated calcium channel

    Science.gov (United States)

    Talukdar, Keka; Shantappa, Anil

    2016-05-01

    The naturally occurring proteins that form hole in membrane are commonly known as ion channels. They play multiple roles in many important biological processes. Deletion or alteration of these channels often leads to serious problems in the physiological processes as it controls the flow of ions through it. The proper maintenance of the flow of ions, in turn, is required for normal health. Here we have investigated the behavior of a calcium release-activated calcium ion channel with pdb entry 4HKR in Drosophila Melanogaster. The equilibrium energy as well as molecular dynamics simulation is performed first. The protein is subjected to molecular dynamics simulation to find their energy minimized value. Simulation of the protein in the environment of water and ions has given us important results too. The solvation energy is also found using Charmm potential.

  6. The Calcium Wave of Vegetable Cells

    Directory of Open Access Journals (Sweden)

    TD. Geydan

    2007-08-01

    Full Text Available Calcium is an essential nutrient for plants; it is involved in developmental processes and in responses to biotic and abiotic factors. Several signals that modify the calcium concentration in the cytoplasm, endoplasmic reticulum, nucleus and/or plastids have been observed. These changes in the calcium concentration in the cell interior are rapidly returned to basal levels, in the meantime, innumerable and complex signaling cascades. This note exposes the mechanisms of calcium transport through the cell membranes of the entrance of calcium in the plant cells.

  7. Calcium Intake in the Moroccan Elderly

    Directory of Open Access Journals (Sweden)

    Sebbar El-houcine

    2017-08-01

    Full Text Available Introduction: Calcium intakes of elderly people are often below the recommendations which are 1200 mg/day. The advancing age may be accompanied by a loss of capacity to absorb additional calcium in case of deficiency. The aim of our work is to evaluate the calcium intake in the Moroccan elderly. Methods: The version translated into Arabic dialect Fardellone questionnaire is tested on a sample of 159 subjects aged over 60 years. Results: The study population includes 87 women (55%, 72 men (45%. The mean calcium intake was respectively 3078 mg by week (that means 440 mg/day. The assessment of calcium intake showed a deficiency and the average consumption of calcium per day is significantly lower than the recommended daily amount for this population. The comparison of both gender found a deficit higher among women than among men. Conclusion: Evaluation of the calcium intake is an essential tool for better management of metabolic bone diseases.

  8. Exopolysaccharides regulate calcium flow in cariogenic biofilms.

    Directory of Open Access Journals (Sweden)

    Monika Astasov-Frauenhoffer

    Full Text Available Caries-associated biofilms induce loss of calcium from tooth surfaces in the presence of dietary carbohydrates. Exopolysaccharides (EPS provide a matrix scaffold and an abundance of primary binding sites within biofilms. The role of EPS in binding calcium in cariogenic biofilms is only partially understood. Thus, the aim of the present study is to investigate the relationship between the calcium dissolution rates and calcium tolerance of caries-associated bacteria and yeast as well as to examine the properties of EPS to quantify its binding affinity for dissolved calcium. Calcium dissolution was measured by dissolution zones on Pikovskaya's agar. Calcium tolerance was assessed by isothermal microcalorimetry (IMC by adding CaCl2 to the bacterial cultures. Acid-base titration and Fourier transform infrared (FTIR spectroscopy were used to identify possible functional groups responsible for calcium binding, which was assessed by isothermal titration calorimetry (ITC. Lactobacillus spp. and mutans streptococci demonstrated calcium dissolution in the presence of different carbohydrates. All strains that demonstrated high dissolution rates also revealed higher rates of calcium tolerance by IMC. In addition, acidic functional groups were predominantly identified as possible binding sites for calcium ions by acid-base titration and FTIR. Finally, ITC revealed EPS to have a higher binding affinity for calcium compared, for example, to lactic acid. In conclusion, this study illustrates the role of EPS in terms of the calcium tolerance of cariogenic microbiota by determining the ability of EPS to control free calcium concentrations within the biofilms as a self-regulating mode of action in the pathogenesis of dental caries.

  9. Calcium-dependent smooth muscle excitatory effect elicited by the venom of the hydrocoral Millepora complanata.

    Science.gov (United States)

    Rojas, Alejandra; Torres, Mónica; Rojas, J Isela; Feregrino, Angélica; Heimer-de la Cotera, Edgar P

    2002-06-01

    In the present paper, we describe the results obtained from a preliminary pharmacological and biochemical study of the fire coral Millepora complanata, a regular component of coral reefs in the Mexican Caribbean. The protein-containing crude extract obtained from M. complanata (tested from 0.001 to 1000 microg protein/ml) caused a concentration-dependent stimulation of spontaneous contractions of the guinea pig ileum. The extract (EC(50)=11.55+/-2.36 microg/ml) was approximately 12-fold less potent than ionomycin (EC(50)=0.876+/-0.25 microg/ml) and its maximum induced contraction (1mg protein/ml) was equivalent to 68% of the response to 60mM KCl. FPLC size exclusion chromatography of the M. complanta extract afforded 12 primary fractions, of which only FV (containing proteins with molecular weights ranging from 17 to 44 kDa) and FVIII (consisting of peptides with molecular weights lesser than 1.8k Da) elicited an excitatory effect when tested at the EC(50) of the original extract. After incubation in Ca(2+)-free medium, the ileal response to FV and FVIII was significantly reduced. Blockage of L-type Ca(2+) channels with nifedipine (1 microM) inhibited FV and FVIII-evoked contractions. Cd(2+) (10 microM), an unspecific blocker of voltage-activated calcium channels, also antagonized FV and FVIII-induced effects, whereas the Na(+) channel blocker tetrodotoxin (10nM) did not significantly affect FV and FVIII responses. These results suggest that the contractions induced by the bioactive fractions obtained from the crude extract of M. complanata are caused mainly by a direct action on smooth muscle cells, via an increase in Ca(2+) permeability that occurs, at least partly, through L-type voltage-dependent Ca(2+) channels found in the cell membrane of smooth muscle. Copright 2002 Elsevier Science Ltd.

  10. [Reconstitution of large conductance calcium-activated potassium channels into artificial planar lipid bilayers].

    Science.gov (United States)

    Cheng, Jun; Zeng, Xiao-Rong; Tan, Xiao-Qiu; Li, Peng-Yun; Wen, Jing; Mao, Liang; Yang, Yan

    2017-06-25

    This study was aimed to establish a method to create a stable planar lipid bilayer membranes (PLBMs), in which large conductance calcium-activated potassium channels (BK Ca ) were reconstituted. Using spreading method, PLBMs were prepared by decane lipid fluid consisting of N 2 -weathered mixture of phosphatidylcholine and cholesterol at 3:1 ratio. After successful incorporation of BK Ca channel into PLBMs, single channel characteristics of BK Ca were studied by patch clamp method. The results showed that i) the single channel conductance of BK Ca was (206.8 ± 16.9) pS; ii) the activities of BK Ca channel were voltage dependent; iii) in the bath solution without Ca 2+ , there was almost no BK Ca channel activities regardless of under hyperpolarization or repolarization conditions; iv) under the condition of +40 mV membrane potential, BK Ca channels were activated in a Ca 2+ concentration dependent manner; v) when [Ca 2+ ] was increased from 1 μmol/L to 100 μmol/L, both the channel open probability and the average open time were increased, and the average close time was decreased from (32.2 ± 2.8) ms to (2.1 ± 1.8) ms; vi) the reverse potential of the reconstituted BK Ca was -30 mV when [K + ] was at 40/140 mmol/L (Cis/Trans). These results suggest that the spreading method could serve as a new method for preparing PLBMs and the reconstituted BK Ca into PLBMs showed similar electrophysiological characteristics to natural BK Ca channels, so the PLBMs with incorporated BK Ca can be used in the studies of pharmacology and dynamics of BK Ca channel.

  11. Trafficking of neuronal calcium channels

    Czech Academy of Sciences Publication Activity Database

    Weiss, Norbert; Zamponi, G. W.

    2017-01-01

    Roč. 1, č. 1 (2017), č. článku NS20160003. ISSN 2059-6553 R&D Projects: GA ČR GA15-13556S; GA MŠk 7AMB15FR015 Institutional support: RVO:61388963 Keywords : calcium channel * neuron * trafficing Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) http://www. neuron alsignaling.org/content/1/1/NS20160003

  12. Compton profile of calcium fluoride

    International Nuclear Information System (INIS)

    Vijayakumar, R.; Rajasekaran, L.; Ramamurthy, N.; Shivaramu

    2003-01-01

    Full text: The Compton profile of polycrystalline calcium fluoride is measured using 661.6 keV γ- radiation from a 137 Cs source. The experimental data are compared with HF-LCAO model calculation computed using CRYSTAL98 program, Hartree-Fock free atom theoretical values and with the other available experimental data. Experimental results are found to be in good agreement with the HF-LCAO model calculations and in qualitative agreement with Hartree-Fock free atom theoretical values

  13. The Role of Calcium in Osteoporosis

    Science.gov (United States)

    Arnaud, C. D.; Sanchez, S. D.

    1991-01-01

    Calcium requirements may vary throughout the lifespan. During the growth years and up to age 25 to 30, it is important to maximize dietary intake of calcium to maintain positive calcium balance and achieve peak bone mass, thereby possibly decreasing the risk of fracture when bone is subsequently lost. Calcium intake need not be greater than 800 mg/day during the relatively short period of time between the end of bone building and the onset of bone loss (30 to 40 years). Starting at age 40 to 50, both men and women lose bone slowly, but women lose bone more rapidly around the menopause and for about 10 years after. Intestinal calcium absorption and the ability to adapt to low calcium diets are impaired in many postmenopausal women and elderly persons owing to a suspected functional or absolute decrease in the ability of the kidney to produce 1,25(OH)2D2. The bones then become more and more a source of calcium to maintain critical extracellular fluid calcium levels. Excessive dietary intake of protein and fiber may induce significant negative calcium balance and thus increase dietary calcium requirements. Generally, the strongest risk factors for osteoporosis are uncontrollable (e.g., sex, age, and race) or less controllable (e.g., disease and medications). However, several factors such as diet, physical activity, cigarette smoking, and alcohol use are lifestyle related and can be modified to help reduce the risk of osteoporosis.

  14. Calcium Impact on Milk Gels Formation

    DEFF Research Database (Denmark)

    Koutina, Glykeria

    enriched dairy products. Calcium gels can be produced by addition of a calcium salt and heat treatment at temperatures higher than 70 oC for several minutes. The combination of heat treatment and calcium addition to milk with pH values between 6.6 and 5.6, will produce calcium milk gels with unique...... and dense gel structure and with little seperation of whey due to participation of calcium to the final gel structure. On the other hand, the combination of heat treatment and calcium addition to milk with pH values lower than 5.6 will still produce gel structures which are dominated by the decrease of p...... to be formed. In addition the low amount of micellar calcium caused a more compact gel structure with many protein aggregates. The results of this study highlighted the importance of calcium for the formation of acid, calcium and rennet gels. The content and the interactions of calcium with proteins during...

  15. Rapid screening assay for calcium bioavailability studies

    International Nuclear Information System (INIS)

    Luhrsen, K.R.; Hudepohl, G.R.; Smith, K.T.

    1986-01-01

    Calcium bioavailability has been studied by numerous techniques. The authors report here the use of the gamma emitting isotope of calcium ( 47 Ca) in a whole body retention assay system. In this system, calcium sources are administered by oral gavage and subsequent counts are determined and corrected for isotopic decay. Unlike iron and zinc retention curves, which exhibit a 2-3 day equilibration period, calcium reaches equilibration after 24 hours. Autoradiographic analysis of the femurs indicate that the newly absorbed calcium is rapidly distributed to the skeletal system. Moreover, the isotope is distributed along the entire bone. Comparisons of calcium bioavailability were made using intrinsic/extrinsic labeled milk from two species i.e. rat and goat as well as CaCO 3 . In addition, extrinsic labeled cow milk was examined. In the rat, the extrinsic labeled calcium from milk was better absorbed than the intrinsic calcium. This was not the case in goat milk or the calcium carbonate which exhibited no significant differences. Chromatographic analysis of the labeled milk indicates a difference in distribution of the 47 Ca. From these data, the authors recommend the use of this assay system in calcium bioavailability studies. The labeling studies and comparisons indicate caution should be used, however, in labeling techniques and species milk comparison

  16. The Risks and Benefits of Calcium Supplementation

    Directory of Open Access Journals (Sweden)

    Chan Soo Shin

    2015-03-01

    Full Text Available The association between calcium supplementation and adverse cardiovascular events has recently become a topic of debate due to the publication of two epidemiological studies and one meta-analysis of randomized controlled clinical trials. The reports indicate that there is a significant increase in adverse cardiovascular events following supplementation with calcium; however, a number of experts have raised several issues with these reports such as inconsistencies in attempts to reproduce the findings in other populations and questions concerning the validity of the data due to low compliance, biases in case ascertainment, and/or a lack of adjustment. Additionally, the Auckland Calcium Study, the Women's Health Initiative, and many other studies included in the meta-analysis obtained data from calcium-replete subjects and it is not clear whether the same risk profile would be observed in populations with low calcium intakes. Dietary calcium intake varies widely throughout the world and it is especially low in East Asia, although the risk of cardiovascular events is less prominent in this region. Therefore, clarification is necessary regarding the occurrence of adverse cardiovascular events following calcium supplementation and whether this relationship can be generalized to populations with low calcium intakes. Additionally, the skeletal benefits from calcium supplementation are greater in subjects with low calcium intakes and, therefore, the risk-benefit ratio of calcium supplementation is likely to differ based on the dietary calcium intake and risks of osteoporosis and cardiovascular diseases of various populations. Further studies investigating the risk-benefit profiles of calcium supplementation in various populations are required to develop population-specific guidelines for individuals of different genders, ages, ethnicities, and risk profiles around the world.

  17. Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients

    OpenAIRE

    Eder, Anja; Bading, Hilmar

    2007-01-01

    Abstract Background In hippocampal neurons, nuclear calcium signaling is important for learning- and neuronal survival-associated gene expression. However, it is unknown whether calcium signals generated by neuronal activity at the cell membrane and propagated to the soma can unrestrictedly cross the nuclear envelope to invade the nucleus. The nuclear envelope, which allows ion transit via the nuclear pore complex, may represent a barrier for calcium and has been suggested to insulate the nuc...

  18. Intracellular Calcium Mobilization in Response to Ion Channel Regulators via a Calcium-Induced Calcium Release Mechanism

    OpenAIRE

    Petrou, Terry; Olsen, Herv?r L.; Thrasivoulou, Christopher; Masters, John R.; Ashmore, Jonathan F.; Ahmed, Aamir

    2017-01-01

    Free intracellular calcium ([Ca2+]i), in addition to being an important second messenger, is a key regulator of many cellular processes including the cell membrane potential, proliferation and apoptosis. In many cases, the mobilization of [Ca2+]i is controlled by intracellular store activation and calcium influx. We have investigated the effect of several ion channel modulators, which have been used to treat a range of human diseases, on [Ca2+]i release, by ratiometric calcium imaging. We sho...

  19. Store-Operated Calcium Entry in Müller Glia Is Controlled by Synergistic Activation of TRPC and Orai Channels

    Science.gov (United States)

    Molnár, Tünde; Yarishkin, Oleg; Iuso, Anthony; Barabas, Peter; Jones, Bryan; Marc, Robert E.; Phuong, Tam T.T.

    2016-01-01

    The endoplasmic reticulum (ER) is at the epicenter of astrocyte Ca2+ signaling. We sought to identify the molecular mechanism underlying store-operated calcium entry that replenishes ER stores in mouse Müller cells. Store depletion, induced through blockade of sequestration transporters in Ca2+-free saline, induced synergistic activation of canonical transient receptor potential 1 (TRPC1) and Orai channels. Store-operated TRPC1 channels were identified by their electrophysiological properties, pharmacological blockers, and ablation of the Trpc1 gene. Ca2+ release-activated currents (ICRAC) were identified by ion permeability, voltage dependence, and sensitivity to selective Orai antagonists Synta66 and GSK7975A. Depletion-evoked calcium influx was initiated at the Müller end-foot and apical process, triggering centrifugal propagation of Ca2+ waves into the cell body. EM analysis of the end-foot compartment showed high-density ER cisternae that shadow retinal ganglion cell (RGC) somata and axons, protoplasmic astrocytes, vascular endothelial cells, and ER–mitochondrial contacts at the vitreal surface of the end-foot. The mouse retina expresses transcripts encoding both Stim and all known Orai genes; Müller glia predominantly express stromal interacting molecule 1 (STIM1), whereas STIM2 is mainly confined to the outer plexiform and RGC layers. Elimination of TRPC1 facilitated Müller gliosis induced by the elevation of intraocular pressure, suggesting that TRPC channels might play a neuroprotective role during mechanical stress. By characterizing the properties of store-operated signaling pathways in Müller cells, these studies expand the current knowledge about the functional roles these cells play in retinal physiology and pathology while also providing further evidence for the complexity of calcium signaling mechanisms in CNS astroglia. SIGNIFICANCE STATEMENT Store-operated Ca2+ signaling represents a major signaling pathway and source of cytosolic Ca2+ in

  20. Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients

    Directory of Open Access Journals (Sweden)

    Bading Hilmar

    2007-07-01

    Full Text Available Abstract Background In hippocampal neurons, nuclear calcium signaling is important for learning- and neuronal survival-associated gene expression. However, it is unknown whether calcium signals generated by neuronal activity at the cell membrane and propagated to the soma can unrestrictedly cross the nuclear envelope to invade the nucleus. The nuclear envelope, which allows ion transit via the nuclear pore complex, may represent a barrier for calcium and has been suggested to insulate the nucleus from activity-induced cytoplasmic calcium transients in some cell types. Results Using laser-assisted uncaging of caged calcium compounds in defined sub-cellular domains, we show here that the nuclear compartment border does not represent a barrier for calcium signals in hippocampal neurons. Although passive diffusion of molecules between the cytosol and the nucleoplasm may be modulated through changes in conformational state of the nuclear pore complex, we found no evidence for a gating mechanism for calcium movement across the nuclear border. Conclusion Thus, the nuclear envelope does not spatially restrict calcium transients to the somatic cytosol but allows calcium signals to freely enter the cell nucleus to trigger genomic events.

  1. Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients

    Science.gov (United States)

    Eder, Anja; Bading, Hilmar

    2007-01-01

    Background In hippocampal neurons, nuclear calcium signaling is important for learning- and neuronal survival-associated gene expression. However, it is unknown whether calcium signals generated by neuronal activity at the cell membrane and propagated to the soma can unrestrictedly cross the nuclear envelope to invade the nucleus. The nuclear envelope, which allows ion transit via the nuclear pore complex, may represent a barrier for calcium and has been suggested to insulate the nucleus from activity-induced cytoplasmic calcium transients in some cell types. Results Using laser-assisted uncaging of caged calcium compounds in defined sub-cellular domains, we show here that the nuclear compartment border does not represent a barrier for calcium signals in hippocampal neurons. Although passive diffusion of molecules between the cytosol and the nucleoplasm may be modulated through changes in conformational state of the nuclear pore complex, we found no evidence for a gating mechanism for calcium movement across the nuclear border. Conclusion Thus, the nuclear envelope does not spatially restrict calcium transients to the somatic cytosol but allows calcium signals to freely enter the cell nucleus to trigger genomic events. PMID:17663775

  2. WAYS TO CORRECT CALCIUM DEFFICIT AMONG CHILDREN

    Directory of Open Access Journals (Sweden)

    N.I. Taibulatov

    2007-01-01

    Full Text Available The article is dedicated to the urgent issue of the pediatrics — calcium deficit among children. The authors provide modern data on the scheme of the normal calcium exchange in the human body. They also review the main diseases related to the disorders of the pho sphorocalcic metabolism, requiring prompt prevention and treatment by calcium based medications. The researchers stress the diseases of the musculoskeletal system, as insufficient calcium, phosphorus and vitamins supply of the child's body chiefly effects the state of the skeletal and muscular tissue. They give recommendations how to use the vitamin and mineral complex to correct calcium deficit.Key words: calcium deficit, diseases of the musculoskeletal system, vitamin and mineral complex, children.

  3. Store-Operated Calcium Channel and Cancer

    OpenAIRE

    Yang S; Chang WC

    2012-01-01

    The increase of intracellular Ca2+ concentration is an important mechanism that regulates a variety of physiological processes ranging from exocytosis to gene regulation and cell proliferation [1]. Calcium release from intracellular stores (mainly endoplasmic reticulum, ER) or calcium entry through calcium channels can be used by cells to evoke a higher level of cytosolic Ca2+ concentration. In non-excitable cells, a major pathway for Ca2+ influx is via store-operated Ca2+ channels (also know...

  4. The Total Synthesis Of Calcium Atorvastatin.

    OpenAIRE

    Dias, Luiz C; Vieira, Adriano S; Barreiro, Eliezer J

    2016-01-01

    A practical and convergent asymmetric route to calcium atorvastatin (1) is reported. The synthesis of calcium atorvastatin (1) was performed using the remote 1,5-anti asymmetric induction in the boron-mediated aldol reaction of β-alkoxy methylketone (4) with pyrrolic aldehyde (3) as a key step. Calcium atorvastatin was obtained from aldehyde (3) after 6 steps, with a 41% overall yield.

  5. The total synthesis of calcium atorvastatin.

    Science.gov (United States)

    Dias, Luiz C; Vieira, Adriano S; Barreiro, Eliezer J

    2016-02-21

    A practical and convergent asymmetric route to calcium atorvastatin (1) is reported. The synthesis of calcium atorvastatin (1) was performed using the remote 1,5-anti asymmetric induction in the boron-mediated aldol reaction of β-alkoxy methylketone (4) with pyrrolic aldehyde (3) as a key step. Calcium atorvastatin was obtained from aldehyde (3) after 6 steps, with a 41% overall yield.

  6. Calcium and magnesium silicate hydrates

    International Nuclear Information System (INIS)

    Lothenbach, B.; L'Hopital, E.; Nied, D.; Achiedo, G.; Dauzeres, A.

    2015-01-01

    Deep geological disposals are planed to discard long-lived intermediate-level and high-level radioactive wastes. Clay-based geological barriers are expected to limit the ingress of groundwater and to reduce the mobility of radioelements. In the interaction zone between the cement and the clay based material alteration can occur. Magnesium silicate hydrates (M-S-H) have been observed due to the reaction of magnesium sulfate containing groundwater with cements or in the interaction zone between low-pH type cement and clays. M-S-H samples synthesized in the laboratory showed that M-S-H has a variable composition within 0.7 ≤ Mg/Si ≤ 1.5. TEM/EDS analyses show an homogeneous gel with no defined structure. IR and 29 Si NMR data reveal a higher polymerization degree of the silica network in M-S-H compared to calcium silicate hydrates (C-S-H). The presence of mainly Q 3 silicate tetrahedrons in M-S-H indicates a sheet like or a triple-chain silica structure while C-S-H is characterised by single chain-structure. The clear difference in the silica structure and the larger ionic radius of Ca 2+ (1.1 Angstrom) compared to Mg 2+ (0.8 Angstrom) make the formation of an extended solid solution between M-S-H and C-S-H gel improbable. In fact, the analyses of synthetic samples containing both magnesium and calcium in various ratios indicate the formation of separate M-S-H and C-S-H gels with no or very little uptake of magnesium in CS-H or calcium in M-S-H

  7. Calcium

    Science.gov (United States)

    ... Building Bones Print You probably heard "drink your milk" all the time from your parents when you were a kid, and you knew it was good for you. But now you may opt for sodas or sports drinks, and other than adding a splash to ... much thought to milk. But your parents were right to make you ...

  8. Calcium dependence of inactivation of calcium release from the sarcoplasmic reticulum in skeletal muscle fibers.

    Science.gov (United States)

    Simon, B J; Klein, M G; Schneider, M F

    1991-03-01

    The steady-state calcium dependence of inactivation of calcium release from the sarcoplasmic reticulum was studied in voltage-clamped, cut segments of frog skeletal muscle fibers containing two calcium indicators, fura-2 and anti-pyrylazo III (AP III). Fura-2 fluorescence was used to monitor resting calcium and relatively small calcium transients during small depolarizations. AP III absorbance signals were used to monitor larger calcium transients during larger depolarizations. The rate of release (Rrel) of calcium from the sarcoplasmic reticulum was calculated from the calcium transients. The equilibrium calcium dependence of inactivation of calcium release was determined using 200-ms prepulses of various amplitudes to elevate [Ca2+] to various steady levels. Each prepulse was followed by a constant test pulse. The suppression of peak Rrel during the test pulse provided a measure of the extent of inactivation of release at the end of the prepulse. The [Ca2+] dependence of inactivation indicated that binding of more than one calcium ion was required to inactivate each release channel. Half-maximal inactivation was produced at a [Ca2+] of approximately 0.3 microM. Variation of the prepulse duration and amplitude showed that the suppression of peak release was consistent with calcium-dependent inactivation of calcium release but not with calcium depletion. The same calcium dependence of inactivation was obtained using different amplitude test pulses to determine the degree of inactivation. Prepulses that produced near maximal inactivation of release during the following test pulse produced no suppression of intramembrane charge movement during the test pulse, indicating that inactivation occurred at a step beyond the voltage sensor for calcium release. Three alternative set of properties that were assumed for the rapidly equilibrating calcium-binding sites intrinsic to the fibers gave somewhat different Rrel records, but gave very similar calcium dependence of

  9. The Electronic Structure of Calcium

    DEFF Research Database (Denmark)

    Jan, J.-P.; Skriver, Hans Lomholt

    1981-01-01

    The electronic structure of calcium under pressure is re-examined by means of self-consistent energy band calculations based on the local density approximation and using the linear muffin-tin orbitals (LMTO) method with corrections to the atomic sphere approximation included. At zero pressure.......149 Ryd, respectively, relative to the s band, give the best possible agreement. Under increasing pressure the s and p electrons are found to transfer into the d band, and Ca undergoes metal-semimetal-metal electronic transitions. Calculations of the bandstructure and the electronic pressure, including...

  10. [Calcium hypothesis of Alzheimer disease].

    Science.gov (United States)

    Riazantseva, M A; Mozhaeva, G N; Kaznacheeva, E V

    2012-01-01

    Alzheimer's disease is the most common neurodegenerative disorder characterized by progressive memory and cognitive abilities loss. The etiology of Alzheimer's disease is poorly understood. In this regard, there is no effective treatment for the disease. Various hypotheses to explain the nature of the pathology of Alzheimer's disease led to the development of appropriate therapeutics. Despite of decades of research and clinical trials available therapeutics, at best, can only slow down the progression of the disease, but cannot cure it. This review dedicated to the one of modern hypotheses of Alzheimer's disease pathogenesis implied the impairment of calcium homeostasis as a key event for the development of neurodegenerative processes.

  11. Diuretics and disorders of calcium homeostasis.

    Science.gov (United States)

    Grieff, Marvin; Bushinsky, David A

    2011-11-01

    Diuretics commonly are administered in disorders of sodium balance. Loop diuretics inhibit the Na-K-2Cl transporter and also increase calcium excretion. They are often used in the treatment of hypercalcemia. Thiazide diuretics block the thiazide-sensitive NaCl transporter in the distal convoluted tubule, and can decrease calcium excretion. They are often used in the treatment of nephrolithiasis. Carbonic anhydrase inhibitors decrease bicarbonate absorption and the resultant metabolic acidosis can increase calcium excretion. Their use can promote nephrocalcinosis and nephrolithiasis. This review will address the use of diuretics on disorders of calcium homeostasis. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Calcium channel blockers and prostate cancer.

    Science.gov (United States)

    Loughlin, Kevin R

    2014-07-01

    The relationship between calcium channel blockers and prostate cancer has been an area of increased interest to investigators. Calcium channel blockers have been shown to influence cell proliferation, differentiation, and apoptosis. Clinically, the association between calcium channel blockers and the development of prostate cancer has been controversial. However, on a basic science level, there is evidence that calcium channel blockers induce cytotoxicity in androgen receptor positive cell lines and may offer an innovative strategy for the treatment of castration-resistant prostate cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Short communication: Urinary oxalate and calcium excretion by dogs and cats diagnosed with calcium oxalate urolithiasis

    NARCIS (Netherlands)

    Dijcker, J.C.; Kummeling, A.; Hagen-Plantinga, E.A.; Hendriks, W.H.

    2012-01-01

    Introduction Urine concentrations of oxalate and calcium play an important role in calcium oxalate (CaOx) urolith formation in dogs and cats, with high excretions of both substances increasing the chance of CaOx urolithiasis. In 17 CaOx-forming dogs, urine calcium:creatinine ratio (Ca:Cr) was found

  14. 21 CFR 172.330 - Calcium pantothenate, calcium chloride double salt.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium pantothenate, calcium chloride double salt... SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.330 Calcium pantothenate...

  15. An overview of techniques for the measurement of calcium distribution, calcium fluxes, and cytosolic free calcium in mammalian cells

    International Nuclear Information System (INIS)

    Borle, A.B.

    1990-01-01

    An array of techniques can be used to study cell calcium metabolism that comprises several calcium compartments and many types of transport systems such as ion channels, ATP-dependent pumps, and antiporters. The measurement of total call calcium brings little information of value since 60 to 80% of total cell calcium is actually bound to the extracellular glycocalyx. Cell fractionation and differential centrifugation have been used to study intracellular Ca 2+ compartmentalization, but the methods suffer from the possibility of Ca 2+ loss or redistribution among cell fractions. Steady-state kinetic analyses of 45 Ca uptake or desaturation curves have been used to study the distribution of Ca 2+ among various kinetic pools in living cells and their rate of Ca 2+ exchange, but the analyses are constrained by many limitations. Nonsteady-state tracer studies can provide information about rapid changes in calcium influx or efflux in and out of the cell. Zero-time kinetics of 45 Ca uptake can detect instantaneous changes in calcium influx, while 45 Ca fractional efflux ratio, can detect rapid stimulations or inhibitions of calcium efflux out of cells. The best strategy to study cell calcium metabolism is to use several different methods that focus on a specific problem from widely different angles

  16. Codissolution of calcium hydrogenphosphate and sodium hydrogencitrate in water. Spontaneous supersaturation of calcium citrate increasing calcium bioavailability

    DEFF Research Database (Denmark)

    Hedegaard, Martina Vavrusova; Danielsen, Bente Pia; Garcia, André Castilho

    2018-01-01

    . The supersaturated solutions had a pH around 4.7, and calcium binding to hydrogencitrate as the dominant citrate species during precipitation was found to be exothermic with a determined association constant of 357 L mol-1 at 25 °C for unit ionic strength, and δH° = -22 ± 2 kJ mol-1, δS° = -26 ± 8 J K-1 mol-1......The sparingly soluble calcium hydrogenphosphate dihydrate, co-dissolving in water during dissolution of freely soluble sodium hydrogencitrate sesquihydrate as caused by proton transfer from hydrogencitrate to hydrogenphosphate, was found to form homogenous solutions supersaturated by a factor up...... to 8 in calcium citrate tetrahydrate. A critical hydrogencitrate concentration for formation of homogeneous solutions was found to depend linearly on dissolved calcium hydrogenphosphate: [HCitr2-] = 14[CaHPO4] - 0.05 at 25 °C. The lag phase for precipitation of calcium citrate tetrahydrate...

  17. Chapter 9: Model Systems for Formation and Dissolution of Calcium Phosphate Minerals

    Energy Technology Data Exchange (ETDEWEB)

    Orme, C A; Giocondi, J L

    2006-07-29

    Calcium phosphates are the mineral component of bones and teeth. As such there is great interest in understanding the physical mechanisms that underlie their growth, dissolution, and phase stability. Control is often achieved at the cellular level by the manipulation of solution states and the use of crystal growth modulators such as peptides or other organic molecules. This chapter begins with a discussion of solution speciation in body fluids and relates this to important crystal growth parameters such as the supersaturation, pH, ionic strength and the ratio of calcium to phosphate activities. We then discuss the use of scanning probe microscopy as a tool to measure surface kinetics of mineral surfaces evolving in simplified solutions. The two primary themes that we will touch on are the use of microenvironments that temporally evolve the solution state to control growth and dissolution; and the use of various growth modifiers that interact with the solution species or with mineral surfaces to shift growth away from the lowest energy facetted forms. The study of synthetic minerals in simplified solution lays the foundation for understand mineralization process in more complex environments found in the body.

  18. Fast kinetics of calcium dissociation from calsequestrin

    Directory of Open Access Journals (Sweden)

    MARIANELA BELTRÁN

    2006-01-01

    Full Text Available We measured the kinetics of calcium dissociation from calsequestrin in solution or forming part of isolated junctional sarcoplasmic reticulum membranes by mixing calsequestrin equilibrated with calcium with calcium-free solutions in a stopped-flow system. In parallel, we measured the kinetics of the intrinsic fluorescence changes that take place following calcium dissociation from calsequestrin. We found that at 25ºC calcium dissociation was 10-fold faster for calsequestrin attached to junctional membranes (k = 109 s-1 than in solution. These results imply that calcium dissociation from calsequestrin in vivo is not rate limiting during excitation-contraction coupling. In addition, we found that the intrinsic fluorescence decrease for calsequestrin in solution or forming part of junctional membranes was significantly slower than the rates of calcium dissociation. The kinetics of intrinsic fluorescence changes had two components for calsequestrin associated to junctional membranes and only one for calsequestrin in solution; the faster component was 8-fold faster (k = 54.1 s-1 than the slower component (k = 6.9 s-1, which had the same k value as for calsequestrin in solution. These combined results suggest that the presence of calsequestrin at high concentrations in a restricted space, such as when bound to the junctional membrane, accelerates calcium dissociation and the resulting structural changes, presumably as a result of cooperative molecular interactions.

  19. ALG-2, a multifunctional calcium binding protein?

    DEFF Research Database (Denmark)

    Tarabykina, Svetlana; Mollerup, Jens; Winding Gojkovic, P.

    2004-01-01

    ALG-2 was originally discovered as a pro-apoptotic protein in a genetic screen. Due to its ability to bind calcium with high affinity it was postulated to provide a link between the known effect of calcium in programmed cell death and the molecular death execution machinery. This review article d...

  20. Interaction between Vitamin D and calcium

    NARCIS (Netherlands)

    Lips, P.T.A.M.

    2012-01-01

    A low calcium intake aggravates the consequences of vitamin D deficiency. This suggests an interaction between vitamin D and calcium intake, which is the subject of this review. The active vitamin D metabolite, 1,25-dihydroxyvitamin D (1,25(OH)

  1. Comparison of Serum Calcium and Magnesium Between ...

    African Journals Online (AJOL)

    Background: Evidence suggests the involvement of calcium and magnesium metabolism in the pathophysiology of preeclampsia. However, findings from studies are heterogenous and inconsistent. Aim: The study aimed to compare the total serum calcium and magnesium levels in preeclamptic women with that of ...

  2. Calcium supplementation in osteoporosis: useful or harmful?

    Science.gov (United States)

    Chiodini, Iacopo; Bolland, Mark J

    2018-04-01

    Osteoporosis and fragility fractures are important social and economic problems worldwide and are due to both the loss of bone mineral density and sarcopenia. Indeed, fragility fractures are associated with increased disability, morbidity and mortality. It is known that a normal calcium balance together with a normal vitamin D status is important for maintaining well-balanced bone metabolism, and for many years, calcium and vitamin D have been considered crucial in the prevention and treatment of osteoporosis. However, recently, the usefulness of calcium supplementation (alone or with concomitant vitamin D) has been questioned, since some studies reported only weak efficacy of these supplementations in reducing fragility fracture risk. On the other hand, besides the gastrointestinal side effects of calcium supplements and the risk of kidney stones related to use of co-administered calcium and vitamin D supplements, other recent data suggested potential adverse cardiovascular effects from calcium supplementation. This debate article is focused on the evidence regarding both the possible usefulness for bone health and the potential harmful effects of calcium and/or calcium with vitamin D supplementation. © 2018 European Society of Endocrinology.

  3. 21 CFR 182.3225 - Calcium sorbate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium sorbate. 182.3225 Section 182.3225 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Chemical Preservatives § 182.3225 Calcium...

  4. Calcium, snails, and birds: a case study

    Directory of Open Access Journals (Sweden)

    R. Mänd

    2000-10-01

    Full Text Available Recent studies have shown that wild birds breeding in acidified areas have difficulties with obtaining sufficient calcium for their eggshells, and that the cause of it is the shortage of land snails. Many birds have to search for Ca-rich snail shells on a daily basis during egg production. Molluscs depend on litter calcium, which has decreased due to acidification of the environment. Calcium limitation may be a widespread phenomenon also in non-acidified, naturally Ca-poor areas. The problem is that while in the latter areas the time for development of specific adaptations may have been sufficient, then in acidified areas, on the contrary, calcium shortage is a recent phenomenon. Therefore, since the extent of calcium limitation in non-acidified areas is hard to derive from observational data, experimental approach is needed. We provide experimental evidence that specific calcium deficit does affect reproductive traits also in the birds breeding in naturally base-poor habitats. Our study was conducted in a heterogeneous woodland area in Estonia containing deciduous forest patches as well as base-poor pine forest with low snail abundance. Ca supplementation, using snail shell and chicken eggshell fragments, was carried out for pied flycatchers and great tits. Extra calcium affected positively several reproductive traits like egg volume and eggshell thickness, start of breeding, and fledglings’ parameters. The negative relationship between calcium availability and lay-date suggests that birds adjust their breeding tactics to conditions of Ca deficiency, for example, by postponing laying.

  5. Serum Calcium, Inorganic Phosphates and some Haematological ...

    African Journals Online (AJOL)

    Serum calcium level was determined by EDTA titration, inorganic phosphate by spectrophotometric method of Goldberg and the Haematological parameters by Bain method. Results: The age range of both test subjects and controls was 3 to 26 years. There were no significant differences in calcium and inorganic phosphate ...

  6. Physicochemical characterization of zinc-substituted calcium ...

    Indian Academy of Sciences (India)

    Zinc embedded into calcium phosphate may enhance the bone formation and in addition exhibits antifungal and antibacterial properties. Therefore, it is rational to form structures incorporated with this ion. In this paper the incorporation of the Zn ions into natural and synthetic calcium phosphates has been reported.Natural ...

  7. Calcium Orthophosphates in Nature, Biology and Medicine

    Directory of Open Access Journals (Sweden)

    Sergey V. Dorozhkin

    2009-04-01

    Full Text Available The present overview is intended to point the readers’ attention to the important subject of calcium orthophosphates. These materials are of the special significance because they represent the inorganic part of major normal (bones, teeth and dear antlers and pathological (i.e. those appearing due to various diseases calcified tissues of mammals. Due to a great chemical similarity with the biological calcified tissues, many calcium orthophosphates possess remarkable biocompatibility and bioactivity. Materials scientists use this property extensively to construct artificial bone grafts that are either entirely made of or only surface-coated with the biologically relevant calcium orthophosphates. For example, self-setting hydraulic cements made of calcium orthophosphates are helpful in bone repair, while titanium substitutes covered by a surface layer of calcium orthophosphates are used for hip joint endoprostheses and as tooth substitutes. Porous scaffolds made of calcium orthophosphates are very promising tools for tissue engineering applications. In addition, technical grade calcium orthophosphates are very popular mineral fertilizers. Thus ere calcium orthophosphates are of great significance for humankind and, in this paper, an overview on the current knowledge on this subject is provided.

  8. 21 CFR 182.1217 - Calcium phosphate.

    Science.gov (United States)

    2010-04-01

    ... HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food Substances § 182.1217 Calcium phosphate. (a) Product. Calcium phosphate (mono-, di-, and tribasic). (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good...

  9. Rates of calcium carbonate removal from soils.

    NARCIS (Netherlands)

    Breemen, van N.; Protz, R.

    1988-01-01

    Mean annual rates of calcium carbonate removal from soils in a subarctic climate estimated from data on two chronosequences of calcareous storm ridges, appeared to be relatively constant through time. Concentrations of dissolved calcium carbonate in the soil solution in the study sites calculated

  10. Stochastic models of intracellular calcium signals

    Energy Technology Data Exchange (ETDEWEB)

    Rüdiger, Sten, E-mail: sten.ruediger@physik.hu-berlin.de

    2014-01-10

    Cellular signaling operates in a noisy environment shaped by low molecular concentrations and cellular heterogeneity. For calcium release through intracellular channels–one of the most important cellular signaling mechanisms–feedback by liberated calcium endows fluctuations with critical functions in signal generation and formation. In this review it is first described, under which general conditions the environment makes stochasticity relevant, and which conditions allow approximating or deterministic equations. This analysis provides a framework, in which one can deduce an efficient hybrid description combining stochastic and deterministic evolution laws. Within the hybrid approach, Markov chains model gating of channels, while the concentrations of calcium and calcium binding molecules (buffers) are described by reaction–diffusion equations. The article further focuses on the spatial representation of subcellular calcium domains related to intracellular calcium channels. It presents analysis for single channels and clusters of channels and reviews the effects of buffers on the calcium release. For clustered channels, we discuss the application and validity of coarse-graining as well as approaches based on continuous gating variables (Fokker–Planck and chemical Langevin equations). Comparison with recent experiments substantiates the stochastic and spatial approach, identifies minimal requirements for a realistic modeling, and facilitates an understanding of collective channel behavior. At the end of the review, implications of stochastic and local modeling for the generation and properties of cell-wide release and the integration of calcium dynamics into cellular signaling models are discussed.

  11. Role of Calcium and Calmodulin in Plant Cell Regulation

    Science.gov (United States)

    Cormier, M. J.

    1983-01-01

    The role of calcium and calmodulin in plant cell regulation is discussed. Experiments are done to discover the level of calcium in plants and animals. The effect of intracellular calcium on photosynthesis is discussed.

  12. Calcium and Vitamin D: Important at Every Age

    Science.gov (United States)

    ... cup 80–500 (varies) Calcium Culprits Although a balanced diet aids calcium absorption, high levels of protein and ... vitamin D. A Complete Osteoporosis Program Remember, a balanced diet rich in calcium and vitamin D is only ...

  13. Calcium Blood Test: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... page: https://medlineplus.gov/labtests/calciumbloodtest.html Calcium Blood Test To use the sharing features on this page, please enable JavaScript. What is a Calcium Blood Test? A calcium blood test measures the amount of ...

  14. Regulation of intestinal calcium absorption by luminal calcium content: role of intestinal alkaline phosphatase.

    Science.gov (United States)

    Brun, Lucas R; Brance, María L; Lombarte, Mercedes; Lupo, Maela; Di Loreto, Verónica E; Rigalli, Alfredo

    2014-07-01

    Intestinal alkaline phosphatase is a brush border enzyme that is stimulated by calcium. Inhibition of intestinal alkaline phosphatase increases intestinal calcium absorption. We hypothesized that intestinal alkaline phosphatase acts as a minute-to-minute regulatory mechanism of calcium entry. The aim of this study was to evaluate the mechanism by which intestinal luminal calcium controls intestinal calcium absorption. We performed kinetic studies with purified intestinal alkaline phosphatase and everted duodenal sacs and showed that intestinal alkaline phosphatase modifies the luminal pH as a function of enzyme concentration and calcium luminal content. A decrease in pH occurred simultaneously with a decrease in calcium absorption. The inhibition of intestinal alkaline phosphatase by l-phenylalanine caused an increase in calcium absorption. This effect was also confirmed in calcium uptake experiments with isolated duodenal cells. Changes in luminal pH arising from intestinal alkaline phosphatase activity induced by luminal calcium concentration modulate intestinal calcium absorption. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Calcium and caffeine interaction in increased calcium balance in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Sandra Tavares da Silva

    2013-06-01

    Full Text Available OBJECTIVE: This study investigated the effects of caffeine intake associated with inadequate or adequate calcium intake in laparotomized or ovariectomized rats by means of the calcium balance. Forty adults Wistar rats were ovariectomized or laparotomized. METHODS: The animals (n=40 were randomly placed in eight groups receiving the AIN-93 diet with 100% or 50% of the recommended calcium intake with or without added caffeine (6mg/kg/day. The animals were kept in individuals metabolic cages at a temperature of 24°±2ºC, light/dark cycles of 12/12 hours, and deionized water available ad libitum. On the 8th week of the experiment, food consumption was measured and 24-hour urine and 4-day feces were collected to determine calcium balance [Balance=Ca intake-(Urinary Ca+Fecal Ca]. RESULTS: Animals with adequate calcium intake presented higher balances and rates of calcium absorption and retention (p<0.05 than those with inadequate calcium intake, regardless of caffeine intake (p<0.05. Caffeine intake did not affect urinary calcium excretion but increased balance (p<0.05 in the groups with adequate calcium intake. CONCLUSION: Adequate calcium intake attenuated the negative effects of estrogen deficiency and improved calcium balance even in the presence of caffeine.

  16. Calcium Phosphates as Delivery Systems for Bisphosphonates

    Directory of Open Access Journals (Sweden)

    Adriana Bigi

    2018-01-01

    Full Text Available Bisphosphonates (BPs are the most utilized drugs for the treatment of osteoporosis, and are usefully employed also for other pathologies characterized by abnormally high bone resorption, including bone metastases. Due to the great affinity of these drugs for calcium ions, calcium phosphates are ideal delivery systems for local administration of BPs to bone, which is aimed to avoid/limit the undesirable side effects of their prolonged systemic use. Direct synthesis in aqueous medium and chemisorptions from solution are the two main routes proposed to synthesize BP functionalized calcium phosphates. The present review overviews the information acquired through the studies on the interaction between bisphosphonate molecules and calcium phosphates. Moreover, particular attention is addressed to some important recent achievements on the applications of BP functionalized calcium phosphates as biomaterials for bone substitution/repair.

  17. Calcium ion currents mediating oocyte maturation events

    Directory of Open Access Journals (Sweden)

    Tosti Elisabetta

    2006-05-01

    Full Text Available Abstract During maturation, the last phase of oogenesis, the oocyte undergoes several changes which prepare it to be ovulated and fertilized. Immature oocytes are arrested in the first meiotic process prophase, that is morphologically identified by a germinal vesicle. The removal of the first meiotic block marks the initiation of maturation. Although a large number of molecules are involved in complex sequences of events, there is evidence that a calcium increase plays a pivotal role in meiosis re-initiation. It is well established that, during this process, calcium is released from the intracellular stores, whereas less is known on the role of external calcium entering the cell through the plasma membrane ion channels. This review is focused on the functional role of calcium currents during oocyte maturation in all the species, from invertebrates to mammals. The emerging role of specific L-type calcium channels will be discussed.

  18. Application of Calcium Phosphate Materials in Dentistry

    Directory of Open Access Journals (Sweden)

    Jabr S. Al-Sanabani

    2013-01-01

    Full Text Available Calcium phosphate materials are similar to bone in composition and in having bioactive and osteoconductive properties. Calcium phosphate materials in different forms, as cements, composites, and coatings, are used in many medical and dental applications. This paper reviews the applications of these materials in dentistry. It presents a brief history, dental applications, and methods for improving their mechanical properties. Notable research is highlighted regarding (1 application of calcium phosphate into various fields in dentistry; (2 improving mechanical properties of calcium phosphate; (3 biomimetic process and functionally graded materials. This paper deals with most common types of the calcium phosphate materials such as hydroxyapatite and tricalcium phosphate which are currently used in dental and medical fields.

  19. The calcium and vitamin D controversy

    DEFF Research Database (Denmark)

    Abrahamsen, Bo

    2017-01-01

    Areas of the world where vitamin D levels are low for months of the year and intakes of calcium are high have a high prevalence of osteoporosis and cardiovascular disease. This suggests a public health message of avoiding calcium supplements and increasing vitamin D intake. No message could be more...... welcome as vitamin D can be given as a bolus while calcium must be taken daily and may be poorly tolerated. This approach is based on no evidence from intervention studies. Randomized controlled trials (RCTs) suggest that vitamin D given with calcium elicits a small reduction in fracture risk and deaths....... This has not been demonstrated for D given alone. The cardiovascular safety of calcium and vitamin D (CaD) supplements is difficult to ascertain due to weaknesses in RCT designs and adjudication that cannot be remedied by subanalysis. Moreover, no major new RCTs are in process to provide better evidence...

  20. [Extracorporeal life support in calcium antagonist intoxication].

    Science.gov (United States)

    Groot, M W; Grewal, S; Meeder, H J; van Thiel, R J; den Uil, C A

    2017-01-01

    Intoxication with calcium antagonists is associated with poor outcome. Even mild calcium antagonist overdose may be fatal. A 51-year-old woman and a 51-year-old man came to the Accident and Emergency Department in severe shock after they had taken a calcium antagonist overdose. After extensive medicinal therapy had failed, they both needed extracorporeal life support (ECLS) as a bridge to recovery. In severe calcium antagonist overdose, the combination of vasoplegia and cardiac failure leads to refractory shock. ECLS temporarily supports the circulation and maintains organ perfusion. In this way ECLS functions as a bridge to recovery and may possibly save lives. Timely consultation with and referral to an ECLS centre is recommended in patients with calcium antagonist overdose.

  1. Presynaptic calcium signalling in cerebellar mossy fibres

    DEFF Research Database (Denmark)

    Thomsen, Louiza Bohn; Jörntell, Henrik; Midtgaard, Jens

    2010-01-01

    affected burst firing in mossy fibres; this paired-pulse depression was reduced by GABA B antagonists. While our results indicated that a presynaptic rosette electrophysiologically functioned as a unit, topical GABA application showed that calcium signals in the branches of complex rosettes could......Whole-cell recordings were obtained from mossy fibre terminals in adult turtles in order to characterize the basic membrane properties. Calcium imaging of presynaptic calcium signals was carried out in order to analyse calcium dynamics and presynaptic GABA B inhibition. A tetrodotoxin (TTX......)-sensitive fast Na(+) spike faithfully followed repetitive depolarizing pulses with little change in spike duration or amplitude, while a strong outward rectification dominated responses to long-lasting depolarizations. High-threshold calcium spikes were uncovered following addition of potassium channel blockers...

  2. [Calcium and vitamin D in osteology].

    Science.gov (United States)

    Amling, M; Barvencik, F

    2015-06-01

    Calcium homeostasis is of paramount physiological and pathophysiological importance in health and disease. This article focuses on the skeletal relevance of calcium and vitamin D in daily clinical practice. Against the background of an endemic vitamin D deficiency in Germany and the increasing number of patients with drug-induced (proton pump inhibitor) enteral calcium uptake problems, it is of critical importance to understand that a vitamin D level of > 30 µg/l (> 75 nmol/l) is required for intact skeletal mineralization and that furthermore, a physiological gastric acid production is essential for a normal enteral uptake of calcium from foodstuffs. Therefore, a guideline-conform handling of vitamin D and calcium substitution is required not only for patients with rheumatoid diseases but also for any osteological therapy.

  3. Oral calcium carbonate affects calcium but not phosphorus balance in stage 3–4 chronic kidney disease

    Science.gov (United States)

    Hill, Kathleen M.; Martin, Berdine R.; Wastney, Meryl; McCabe, George P.; Moe, Sharon M.; Weaver, Connie M.; Peacock, Munro

    2014-01-01

    Chronic kidney disease (CKD) patients are given calcium carbonate to bind dietary phosphorus and reduce phosphorus retention, and to prevent negative calcium balance. Data are limited on calcium and phosphorus balance in CKD to support this. The aim of this study was to determine calcium and phosphorus balance and calcium kinetics with and without calcium carbonate in CKD patients. Eight stage 3/4 CKD patients, eGFR 36 mL/min, participated in two 3-week balances in a randomized placebo-controlled cross-over study of calcium carbonate (1500 mg/d calcium). Calcium and phosphorus balance were determined on a controlled diet. Oral and intravenous 45calcium with blood sampling and urine and fecal collections were used for calcium kinetics. Fasting blood and urine were collected at baseline and end of each week of each balance period for biochemical analyses. Results showed that patients were in neutral calcium and phosphorus balance while on placebo. Calcium carbonate produced positive calcium balance, did not affect phosphorus balance, and produced only a modest reduction in urine phosphorus excretion compared with placebo. Calcium kinetics demonstrated positive net bone balance but less than overall calcium balance suggesting tissue deposition. Fasting biochemistries of calcium and phosphate homeostasis were unaffected by calcium carbonate. If they can be extrapolated to effects of chronic therapy, these data caution against the use of calcium carbonate as a phosphate binder. PMID:23254903

  4. Linking Cellular Mechanisms to Behavior: Entorhinal Persistent Spiking and Membrane Potential Oscillations May Underlie Path Integration, Grid Cell Firing, and Episodic Memory

    Directory of Open Access Journals (Sweden)

    Michael E. Hasselmo

    2008-01-01

    Full Text Available The entorhinal cortex plays an important role in spatial memory and episodic memory functions. These functions may result from cellular mechanisms for integration of the afferent input to entorhinal cortex. This article reviews physiological data on persistent spiking and membrane potential oscillations in entorhinal cortex then presents models showing how both these cellular mechanisms could contribute to properties observed during unit recording, including grid cell firing, and how they could underlie behavioural functions including path integration. The interaction of oscillations and persistent firing could contribute to encoding and retrieval of trajectories through space and time as a mechanism relevant to episodic memory.

  5. Calcium-sensitive immunoaffinity chromatography

    DEFF Research Database (Denmark)

    Henriksen, Maiken L; Lindhardt Madsen, Kirstine; Skjoedt, Karsten

    2014-01-01

    chromatography was superior to the traditional immunoaffinity chromatographies and resulted in a nine-fold improvement of the purification factor. The technique is applicable for the purification of proteins in complex mixtures by single-step fractionation without the denaturation of eluted antigens......Immunoaffinity chromatography is a powerful fractionation technique that has become indispensable for protein purification and characterization. However, it is difficult to retrieve bound proteins without using harsh or denaturing elution conditions, and the purification of scarce antigens...... to homogeneity may be impossible due to contamination with abundant antigens. In this study, we purified the scarce, complement-associated plasma protein complex, collectin LK (CL-LK, complex of collectin liver 1 and kidney 1), by immunoaffinity chromatography using a calcium-sensitive anti-collectin-kidney-1 m...

  6. Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca[superscript 2+]·calmodulins

    Energy Technology Data Exchange (ETDEWEB)

    Fallon, Jennifer L.; Baker, Mariah R.; Xiong, Liangwen; Loy, Ryan E.; Yang, Guojun; Dirksen, Robert T.; Hamilton, Susan L.; Quiocho, Florante A.; (Baylor); (Rochester-Med)

    2009-11-10

    Voltage-dependent calcium channels (Ca(V)) open in response to changes in membrane potential, but their activity is modulated by Ca(2+) binding to calmodulin (CaM). Structural studies of this family of channels have focused on CaM bound to the IQ motif; however, the minimal differences between structures cannot adequately describe CaM's role in the regulation of these channels. We report a unique crystal structure of a 77-residue fragment of the Ca(V)1.2 alpha(1) subunit carboxyl terminus, which includes a tandem of the pre-IQ and IQ domains, in complex with Ca(2+).CaM in 2 distinct binding modes. The structure of the Ca(V)1.2 fragment is an unusual dimer of 2 coiled-coiled pre-IQ regions bridged by 2 Ca(2+).CaMs interacting with the pre-IQ regions and a canonical Ca(V)1-IQ-Ca(2+).CaM complex. Native Ca(V)1.2 channels are shown to be a mixture of monomers/dimers and a point mutation in the pre-IQ region predicted to abolish the coiled-coil structure significantly reduces Ca(2+)-dependent inactivation of heterologously expressed Ca(V)1.2 channels.

  7. Relationship of calcium absorption with 25(OH)D and calcium intake in children with rickets.

    Science.gov (United States)

    Thacher, Tom D; Abrams, Steven A

    2010-11-01

    Nutritional rickets has long been considered a disease caused by vitamin D deficiency, but recent data indicate that inadequate dietary calcium intake is an important cause of rickets, particularly in tropical countries. Children with rickets due to calcium deficiency do not have very low 25(OH)D concentrations, and serum 1,25(OH)(2) D values are markedly elevated. Studies of Nigerian children with rickets demonstrated they have high fractional calcium absorption. A high-phytate diet was demonstrated to increase calcium absorption compared with the fasting state, and enzymatic dephytinization did not significantly improve calcium absorption. When given vitamin D, children with rickets have a marked increase in 1,25(OH)(2) D concentrations without any change in fractional calcium absorption. No positive relationship was found between fractional calcium absorption and serum 25(OH)D concentrations in children on low-calcium diets. More research is needed to understand the interaction between calcium and vitamin D and the role of vitamin D in calcium absorption. © 2010 International Life Sciences Institute.

  8. Production of precipitated calcium carbonate from calcium silicates and carbon dioxide

    International Nuclear Information System (INIS)

    Teir, Sebastian; Eloneva, Sanni; Zevenhoven, Ron

    2005-01-01

    The possibilities for reducing carbon dioxide emissions from the pulp and paper industry by calcium carbonation are presented. The current precipitated calcium carbonate (PCC) production uses mined, crushed calcium carbonate as raw materials. If calcium silicates were used instead, carbon dioxide emissions from the calcination of carbonates would be eliminated. In Finland, there could, thus, be a potential for eliminating 200 kt of carbon dioxide emissions per year, considering only the PCC used in the pulp and paper industry. A preliminary investigation of the feasibility to produce PCC from calcium silicates and the potential to replace calcium carbonate as the raw material was made. Calcium carbonate can be manufactured from calcium silicates by various methods, but only a few have been experimentally verified. The possibility and feasibility of these methods as a replacement for the current PCC production process was studied by thermodynamic equilibrium calculations using HSC software and process modelling using Aspen Plus[reg]. The results from the process modelling showed that a process that uses acetic acid for extraction of the calcium ions is a high potential option for sequestering carbon dioxide by mineral carbonation. The main obstacle seems to be the limited availability and relatively high price of wollastonite, which is a mineral with high calcium silicate content. An alternative is to use the more common, but also more complex, basalt rock instead

  9. Intracellular sphingosine releases calcium from lysosomes

    Science.gov (United States)

    Höglinger, Doris; Haberkant, Per; Aguilera-Romero, Auxiliadora; Riezman, Howard; Porter, Forbes D; Platt, Frances M; Galione, Antony; Schultz, Carsten

    2015-01-01

    To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC. DOI: http://dx.doi.org/10.7554/eLife.10616.001 PMID:26613410

  10. Renoprotective effect of calcium channel blockers

    Directory of Open Access Journals (Sweden)

    Dimković Nada

    2009-01-01

    Full Text Available The advancing chronic renal failure is at most the consequence of secondary haemodynamic and metabolic factors as intraglomerular hypertension and glomerular hypertrophy. Although tight blood pressure control is the major preventive mechanism for progressive renal failure, ACE inhibitors and angiotensin receptor blockers have some other renoprotective mechanisms beyond the blood pressure control. That is why these two groups of antihypertensive drugs traditionally have advantages in treating renal patients especially those with proteinuria over 400-1000 mg/day. Even if earlier experimental studies have shown renoprotective effect of calcium channel blockers, later clinical studies did not prove that calcium channel blockers have any advantages in renal protection over ACE inhibitors given as monotherapy or in combination with ACE inhibitors. It was explained by action of calcium channel blockers on afferent but not on efferent glomerular arterioles; a well known mechanism that leads to intraglomerular hypertension. New generations of dihydropiridine calcium channel blockers can dilate even efferent arterioles not causing unfavorable haemodynamic disturbances. This finding was confirmed in clinical studies which showed that renoprotection established by calcium channel blockers was not inferior to that of ACE inhibitors and that calcium channel blockers and ACE inhibitors have additive effect on renoprotection. Newer generation of dihydropiridine calcium channel blockers seem to offer more therapeutic possibilities in renoprotection by their dual action on afferent and efferent glomerular arterioles and, possibly by other effects beyond the blood pressure control.

  11. Transgenic plants with increased calcium stores

    Science.gov (United States)

    Wyatt, Sarah (Inventor); Tsou, Pei-Lan (Inventor); Robertson, Dominique (Inventor); Boss, Wendy (Inventor)

    2004-01-01

    The present invention provides transgenic plants over-expressing a transgene encoding a calcium-binding protein or peptide (CaBP). Preferably, the CaBP is a calcium storage protein and over-expression thereof does not have undue adverse effects on calcium homeostasis or biochemical pathways that are regulated by calcium. In preferred embodiments, the CaBP is calreticulin (CRT) or calsequestrin. In more preferred embodiments, the CaBP is the C-domain of CRT, a fragment of the C-domain, or multimers of the foregoing. In other preferred embodiments, the CaBP is localized to the endoplasmic reticulum by operatively associating the transgene encoding the CaBP with an endoplasmic reticulum localization peptide. Alternatively, the CaBP is targeted to any other sub-cellular compartment that permits the calcium to be stored in a form that is biologically available to the plant. Also provided are methods of producing plants with desirable phenotypic traits by transformation of the plant with a transgene encoding a CaBP. Such phenotypic traits include increased calcium storage, enhanced resistance to calcium-limiting conditions, enhanced growth and viability, increased disease and stress resistance, enhanced flower and fruit production, reduced senescence, and a decreased need for fertilizer production. Further provided are plants with enhanced nutritional value as human food or animal feed.

  12. Effects of adding chymosin to milk on calcium homeostasis

    DEFF Research Database (Denmark)

    Møller, Ulla Kristine; Jensen, Lars Thorbjørn; Mosekilde, Leif

    2015-01-01

    either chymosin or similar placebo was added. Compared with placebo, chymosin did not affect 24-h urinary calcium, calcium/creatinine ratio, plasma parathyroid hormone, calcitonin or ionized calcium levels. However, during the first 4 h after intake of milk with chymosin, urinary calcium-creatinine ratio...... not depend on plasma 25-hydroxyvitamin D levels. Chymosin added to milk increases renal calcium excretion in the hours following intake without affecting plasma levels of calcium or calciotropic hormones. The effect most likely represents enhanced intestinal calcium absorption shortly after intake. Further......Calcium intake and absorption is important for bone health. In a randomized double-blind cross-over trial, we investigated effects of adding chymosin to milk on the intestinal calcium absorption as measured by renal calcium excretion and indices of calcium homeostasis. The primary outcome...

  13. Chapter 15. Measurement of the main calcium metabolism processes

    International Nuclear Information System (INIS)

    Milhaud, G.

    1975-01-01

    A method of measuring the chief calcium metabolism processes in man is described and is based on the following techniques and theory: intraveinous injection of 45 Ca; determination of the specific radioactivity of serum calcium, total radioactivity of urine and stools, ingested and excreted calcium; mathematical analysis of the specific radioactivity decay curve for serum calcium. The following data were obtained in this way: intestinal absorption fraction of calcium in the chemical state in which it is found in foods; quantity of calcium excreted by the intestin, as distinct from the non-absorbed fraction; physiological turnover rates in the skeleton by osteolysis and osteoblastosis; mass of rapidly exchangeable calcium in the organism, i.e. the calcium pool; rates of exchange with serum calcium of calcium from the different pool components, mass of bone calcium subjected to recrystallisation. Some applications of the method in man and the verification of the theory in rats are reported [fr

  14. Effect of calcium intake on urinary oxalate excretion in calcium stone-forming patients

    Directory of Open Access Journals (Sweden)

    Nishiura J.L.

    2002-01-01

    Full Text Available Dietary calcium lowers the risk of nephrolithiasis due to a decreased absorption of dietary oxalate that is bound by intestinal calcium. The aim of the present study was to evaluate oxaluria in normocalciuric and hypercalciuric lithiasic patients under different calcium intake. Fifty patients (26 females and 24 males, 41 ± 10 years old, whose 4-day dietary records revealed a regular low calcium intake (<=500 mg/day, received an oral calcium load (1 g/day for 7 days. A 24-h urine was obtained before and after load and according to the calciuria under both diets, patients were considered as normocalciuric (NC, N = 15, diet-dependent hypercalciuric (DDHC, N = 9 or diet-independent hypercalciuric (DIHC, N = 26. On regular diet, mean oxaluria was 30 ± 14 mg/24 h for all patients. The 7-day calcium load induced a significant decrease in mean oxaluria compared to the regular diet in NC and DIHC (20 ± 12 vs 26 ± 7 and 27 ± 18 vs 32 ± 15 mg/24 h, respectively, P<0.05 but not in DDHC patients (22 ± 10 vs 23 ± 5 mg/24 h. The lack of an oxalate decrease among DDHC patients after the calcium load might have been due to higher calcium absorption under higher calcium supply, with a consequent lower amount of calcium left in the intestine to bind with oxalate. These data suggest that a long-lasting regular calcium consumption <500 mg was not associated with high oxaluria and that a subpopulation of hypercalciuric patients who presented a higher intestinal calcium absorption (DDHC tended to hyperabsorb oxalate as well, so that oxaluria did not change under different calcium intake.

  15. Nuclear Calcium Buffering Capacity Shapes Neuronal Architecture*

    Science.gov (United States)

    Mauceri, Daniela; Hagenston, Anna M.; Schramm, Kathrin; Weiss, Ursula; Bading, Hilmar

    2015-01-01

    Calcium-binding proteins (CaBPs) such as parvalbumin are part of the cellular calcium buffering system that determines intracellular calcium diffusion and influences the spatiotemporal dynamics of calcium signals. In neurons, CaBPs are primarily localized to the cytosol and function, for example, in nerve terminals in short-term synaptic plasticity. However, CaBPs are also expressed in the cell nucleus, suggesting that they modulate nuclear calcium signals, which are key regulators of neuronal gene expression. Here we show that the calcium buffering capacity of the cell nucleus in mouse hippocampal neurons regulates neuronal architecture by modulating the expression levels of VEGFD and the complement factor C1q-c, two nuclear calcium-regulated genes that control dendrite geometry and spine density, respectively. Increasing the levels of nuclear calcium buffers by means of expression of a nuclearly targeted form of parvalbumin fused to mCherry (PV.NLS-mC) led to a reduction in VEGFD expression and, as a result, to a decrease in total dendritic length and complexity. In contrast, mRNA levels of the synapse pruning factor C1q-c were increased in neurons expressing PV.NLS-mC, causing a reduction in the density and size of dendritic spines. Our results establish a close link between nuclear calcium buffering capacity and the transcription of genes that determine neuronal structure. They suggest that the development of cognitive deficits observed in neurological conditions associated with CaBP deregulation may reflect the loss of necessary structural features of dendrites and spines. PMID:26231212

  16. Calcium Signaling Is Required for Erythroid Enucleation.

    Directory of Open Access Journals (Sweden)

    Christina B Wölwer

    Full Text Available Although erythroid enucleation, the property of erythroblasts to expel their nucleus, has been known for 7ore than a century, surprisingly little is known regarding the molecular mechanisms governing this unique developmental process. Here we show that similar to cytokinesis, nuclear extrusion requires intracellular calcium signaling and signal transduction through the calmodulin (CaM pathway. However, in contrast to cytokinesis we found that orthochromatic erythroblasts require uptake of extracellular calcium to enucleate. Together these functional studies highlight a critical role for calcium signaling in the regulation of erythroid enucleation.

  17. Calcium: A Nutrient Deserving a Special Issue

    Directory of Open Access Journals (Sweden)

    Susan J. Whiting

    2010-10-01

    Full Text Available Interest in calcium has continued since the 1980s when its role in promoting bone growth and retention was established in clinical trials of children and postmenopausal women. The human nutrition functions now attributed to calcium have expanded beyond bone health to include other conditions such as body weight maintenance. While most efforts have been focused on the findings that dietary intakes are low, there are emerging data on safety concerns of excess amounts. This Special Issue on calcium nutrition, spanning the lifecycle from critically ill neonates through to older adults, has been written by some of the leading researchers in this field.

  18. Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium

    Energy Technology Data Exchange (ETDEWEB)

    Wernimont, Amy K; Artz, Jennifer D.; Jr, Patrick Finerty; Lin, Yu-Hui; Amani, Mehrnaz; Allali-Hassani, Abdellah; Senisterra, Guillermo; Vedadi, Masoud; Tempel, Wolfram; Mackenzie, Farrell; Chau, Irene; Lourido, Sebastian; Sibley, L. David; Hui, Raymond (Toronto); (WU-MED)

    2010-09-21

    Calcium-dependent protein kinases (CDPKs) have pivotal roles in the calcium-signaling pathway in plants, ciliates and apicomplexan parasites and comprise a calmodulin-dependent kinase (CaMK)-like kinase domain regulated by a calcium-binding domain in the C terminus. To understand this intramolecular mechanism of activation, we solved the structures of the autoinhibited (apo) and activated (calcium-bound) conformations of CDPKs from the apicomplexan parasites Toxoplasma gondii and Cryptosporidium parvum. In the apo form, the C-terminal CDPK activation domain (CAD) resembles a calmodulin protein with an unexpected long helix in the N terminus that inhibits the kinase domain in the same manner as CaMKII. Calcium binding triggers the reorganization of the CAD into a highly intricate fold, leading to its relocation around the base of the kinase domain to a site remote from the substrate binding site. This large conformational change constitutes a distinct mechanism in calcium signal-transduction pathways.

  19. Intracellular Calcium Mobilization in Response to Ion Channel Regulators via a Calcium-Induced Calcium Release Mechanism.

    Science.gov (United States)

    Petrou, Terry; Olsen, Hervør L; Thrasivoulou, Christopher; Masters, John R; Ashmore, Jonathan F; Ahmed, Aamir

    2017-02-01

    Free intracellular calcium ([Ca 2+ ] i ), in addition to being an important second messenger, is a key regulator of many cellular processes including cell membrane potential, proliferation, and apoptosis. In many cases, the mobilization of [Ca 2+ ] i is controlled by intracellular store activation and calcium influx. We have investigated the effect of several ion channel modulators, which have been used to treat a range of human diseases, on [Ca 2+ ] i release, by ratiometric calcium imaging. We show that six such modulators [amiodarone (Ami), dofetilide, furosemide (Fur), minoxidil (Min), loxapine (Lox), and Nicorandil] initiate release of [Ca 2+ ] i in prostate and breast cancer cell lines, PC3 and MCF7, respectively. Whole-cell currents in PC3 cells were inhibited by the compounds tested in patch-clamp experiments in a concentration-dependent manner. In all cases [Ca 2+ ] i was increased by modulator concentrations comparable to those used clinically. The increase in [Ca 2+ ] i in response to Ami, Fur, Lox, and Min was reduced significantly (P calcium was reduced to nM concentration by chelation with EGTA. The data suggest that many ion channel regulators mobilize [Ca 2+ ] i We suggest a mechanism whereby calcium-induced calcium release is implicated; such a mechanism may be important for understanding the action of these compounds. Copyright © 2017 by The Author(s).

  20. Calcium absorption from fortified ice cream formulations compared with calcium absorption from milk.

    Science.gov (United States)

    van der Hee, Regine M; Miret, Silvia; Slettenaar, Marieke; Duchateau, Guus S M J E; Rietveld, Anton G; Wilkinson, Joy E; Quail, Patricia J; Berry, Mark J; Dainty, Jack R; Teucher, Birgit; Fairweather-Tait, Susan J

    2009-05-01

    Optimal bone mass in early adulthood is achieved through appropriate diet and lifestyle, thereby protecting against osteoporosis and risk of bone fracture in later life. Calcium and vitamin D are essential to build adequate bones, but calcium intakes of many population groups do not meet dietary reference values. In addition, changes in dietary patterns are exacerbating the problem, thereby emphasizing the important role of calcium-rich food products. We have designed a calcium-fortified ice cream formulation that is lower in fat than regular ice cream and could provide a useful source of additional dietary calcium. Calcium absorption from two different ice cream formulations was determined in young adults and compared with milk. Sixteen healthy volunteers (25 to 45 years of age), recruited from the general public of The Netherlands, participated in a randomized, reference-controlled, double-blind cross-over study in which two test products and milk were consumed with a light standard breakfast on three separate occasions: a standard portion of ice cream (60 g) fortified with milk minerals and containing a low level (3%) of butter fat, ice cream (60 g) fortified with milk minerals and containing a typical level (9%) of coconut oil, and reduced-fat milk (1.7% milk fat) (200 mL). Calcium absorption was measured by the dual-label stable isotope technique. Effects on calcium absorption were evaluated by analysis of variance. Fractional absorption of calcium from the 3% butterfat ice cream, 9% coconut oil ice cream, and milk was 26%+/-8%, 28%+/-5%, and 31%+/-9%, respectively, and did not differ significantly (P=0.159). Results indicate that calcium bioavailability in the two calcium-fortified ice cream formulations used in this study is as high as milk, indicating that ice cream may be a good vehicle for delivery of calcium.

  1. Exome sequencing reveals novel rare variants in the ryanodine receptor and calcium channel genes in malignant hyperthermia families.

    Science.gov (United States)

    Kim, Jerry H; Jarvik, Gail P; Browning, Brian L; Rajagopalan, Ramakrishnan; Gordon, Adam S; Rieder, Mark J; Robertson, Peggy D; Nickerson, Deborah A; Fisher, Nickla A; Hopkins, Philip M

    2013-11-01

    About half of malignant hyperthermia (MH) cases are associated with skeletal muscle ryanodine receptor 1 (RYR1) and calcium channel, voltage-dependent, L type, α1S subunit (CACNA1S) gene mutations, leaving many with an unknown cause. The authors chose to apply a sequencing approach to uncover causal variants in unknown cases. Sequencing the exome, the protein-coding region of the genome, has power at low sample sizes and identified the cause of over a dozen Mendelian disorders. The authors considered four families with multiple MH cases lacking mutations in RYR1 and CACNA1S by Sanger sequencing of complementary DNA. Exome sequencing in two affecteds per family, chosen for maximum genetic distance, were compared. Variants were ranked by allele frequency, protein change, and measures of conservation among mammals to assess likelihood of causation. Finally, putative pathogenic mutations were genotyped in other family members to verify cosegregation with MH. Exome sequencing revealed one rare RYR1 nonsynonymous variant in each of three families (Asp1056His, Val2627Met, Val4234Leu), and one CACNA1S variant (Thr1009Lys) in the fourth family. These were not seen in variant databases or in our control population sample of 5,379 exomes. Follow-up sequencing in other family members verified cosegregation of alleles with MH. The authors found that using both exome sequencing and allele frequency data from large sequencing efforts may aid genetic diagnosis of MH. In a sample selected by the authors, this technique was more sensitive for variant detection in known genes than Sanger sequencing of complementary DNA, and allows for the possibility of novel gene discovery.

  2. 21 CFR 184.1185 - Calcium acetate.

    Science.gov (United States)

    2010-04-01

    ... CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific...-4), also known as acetate of lime or vinegar salts, is the calcium salt of acetic acid. It may be...

  3. 21 CFR 172.720 - Calcium lactobionate.

    Science.gov (United States)

    2010-04-01

    ... HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION... additive is the calcium salt of lactobionic acid (4-(β,D-galactosido)-D-gluconic acid) produced by the...

  4. Vitamin D with Calcium Reduces Mortality

    DEFF Research Database (Denmark)

    Rejnmark, Lars; Avenell, Alison; Masud, Tahir

    2012-01-01

    D was given with calcium (hazard ratio, 0.91; 95% CI, 0.84-0.98). The number needed to treat with vitamin D plus calcium for 3 yr to prevent one death was 151. Trial level meta-analysis (24 trials with 88,097 participants) showed similar results, i.e. mortality was reduced with vitamin D plus......Introduction:Vitamin D may affect multiple health outcomes. If so, an effect on mortality is to be expected. Using pooled data from randomized controlled trials, we performed individual patient data (IPD) and trial level meta-analyses to assess mortality among participants randomized to either...... vitamin D alone or vitamin D with calcium.Subjects and Methods:Through a systematic literature search, we identified 24 randomized controlled trials reporting data on mortality in which vitamin D was given either alone or with calcium. From a total of 13 trials with more than 1000 participants each, eight...

  5. Obtainment of calcium carbonate from mussels shell

    International Nuclear Information System (INIS)

    Hamester, M.R.R.; Becker, D.

    2010-01-01

    The mussels and oyster shell are discarded at environment, and this accumulation is causing negative consequences to ecosystem. Calcium carbonate is main constituent of the shell chemical composition. Aiming to reduce environmental aggression and generate income to shellfish producer, there was the possibility of using these shells as an alternative to commercial calcium carbonate. For this physics, chemicals and thermal properties were evaluated, using X-ray fluorescence, thermogravimetric analysis, size distribution, abrasiveness and scanning electronic microscopy. The results indicate that mussels shells have an initial degradation temperature higher than commercial calcium carbonate e same lost weight behavior and 95% of shell chemical composition is calcium carbonate. The sample size distribution was influenced by grinding condition and time as well as its abrasiveness. (author)

  6. Calcium antagonists for aneurysmal subarachnoid haemorrhage

    NARCIS (Netherlands)

    Dorhout Mees, S. M.; Rinkel, G. J. E.; Feigin, V. L.; Algra, A.; van den Bergh, W. M.; Vermeulen, M.; van Gijn, J.

    2007-01-01

    BACKGROUND: Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage (SAH). Its pathogenesis has been incompletely elucidated, but vasospasm probably is a contributing factor. Experimental studies have suggested that calcium antagonists can prevent or reverse

  7. Modeling and analysis of calcium bromide hydrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Lottes, Steven A.; Lyczkowski, Robert W.; Panchal, Chandrakant B.; Doctor, Richard D. [Energy Systems Division, Argonne National Laboratory, 9700 S. Cass Avenue, Argonne, IL 60439 (United States)

    2009-05-15

    The main focus of this paper is the modeling, simulation, and analysis of the calcium bromide hydrolysis reactor stage in the calcium-bromine thermochemical water-splitting cycle for nuclear hydrogen production. One reactor concept is to use a spray of calcium bromide into steam, in which the heat of fusion supplies the heat of reaction. Droplet models were built up in a series of steps incorporating various physical phenomena, including droplet flow, heat transfer, phase change, and reaction, separately. Given the large heat reservoir contained in a pool of molten calcium bromide that allows bubbles to rise easily, using a bubble column reactor for the hydrolysis appears to be a feasible and promising alternative to the spray reactor concept. The two limiting cases of bubble geometry, spherical and spherical-cap, are considered in the modeling. Results for both droplet and bubble modeling with COMSOL MULTIPHYSICS trademark are presented, with recommendations for the path forward. (author)

  8. Can atorvastatin calcium cause asymptomatic hypercalcemia?

    Science.gov (United States)

    Ipekçi, Süleyman Hilmi; Baldane, Süleyman; Sözen, Mehmet; Kebapçılar, Levent

    2014-10-01

    The use of statins may have unnatural effects. A 54-year-old woman was admitted to the hospital with an incidental finding of hypercalcemia (10.8 mg/dL). There was no disease other than hyperlipidemia, and the patient had been on a course of atorvastatin calcium 10 mg for 1.5 years. A workup investigation to diagnose the cause of hypercalcemia was completed. The investigation did not reveal any pathological diseases that may have caused the hypercalcemia. The hypercalcemia resolved after atorvastatin-calcium was stopped, and the patient developed hypercalcemia shortly after the initiation of the atorvastatin calcium. Here, we report a clinical case of recurrent hypercalcemia possibly induced by atorvastatin calcium administration.

  9. 21 CFR 172.120 - Calcium disodium EDTA.

    Science.gov (United States)

    2010-04-01

    ... Food Preservatives § 172.120 Calcium disodium EDTA. The food additive calcium disodium EDTA (calcium... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium disodium EDTA. 172.120 Section 172.120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR...

  10. Does calcium constrain reproductive activity in insectivorous bats ...

    African Journals Online (AJOL)

    Insects are a poor source of dietary calcium and since they are seasonally abundant, it has been suggested that calcium availability may play a significant role in controlling the timing of reproduction in insectivorous bats. To assess the possible role of dietary calcium, we have measured bone calcium concentrations in ...

  11. Enhanced expression of a calcium-dependent protein kinase from ...

    Indian Academy of Sciences (India)

    Unknown

    Calcium-dependent protein kinase; degenerate primer; Funaria hygrometrica; nutrient; polymerase chain reaction; starvation ... Among the downstream targets of calcium in plants, calcium-dependent protein kinases (CDPKs) form an inter- esting class of ..... Saunders M J and Hepler P K 1983 Calcium antagonists and.

  12. [Effect of dietary calcium vs calcium citrate on conventional biochemical markers in perimenopausal women].

    Science.gov (United States)

    Aguilera-Barreiro, Ma de los Angeles; Guerrero-Mercado, Aixa del Socorro; Méndez-Jiménez, Tannia Erika; Milián-Suazo, Feliciano

    2005-01-01

    To compare the effect of calcium citrate and a calcium enriched diet on conventional biochemical markers. Eighty-two women aged 30 to 35 years were randomized to any of three groups:A control group of 23 women who remained intact in their dietary habits and physical activity; a second group of 28 women who received 1000 mg of dietary calcium plus physical activity 30 minutes three times per week; and a third group of 31 women who received 600 mg of calcium citrate plus 500 mg of dietary calcium and physical activity three times per week for seven months. Calcaneum bone densitometry was measured to classify women into normal and osteopenic groups. Biochemical markers were measured at baseline and at the end of the study, as follows: serum alkaline phosphatase, magnesium, calcium and phosphorus, as well as the calcium/creatinine ratio in urine. Thirty-four percent of women were osteopenic. These women showed a significant reduction in the final level of calcium in the third group, as compared to the second group (p Phosphorus levels decreased in the second group (3.5 to 3.2 mg/dl) (p > 0.05). The calcium/creatinine ratio was normal in all groups. The second group showed a higher bone production than the third group. No group showed bone resorption.

  13. The structures of the human calcium channel {alpha}{sub 1} subunit (CACNL1A2) and {beta} subunit (CACNLB3) genes

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Yuichiro; Masuda, Kazuhiro; Li, Qing [Kyoto Univ. Faculty of Medicine (Japan)] [and others

    1995-05-20

    Calcium influx in pancreatic {beta}-cells is regulated mainly by L-type voltage-dependent calcium channels (VDCCs) and triggers insulin secretion. The {alpha}{sub 1} subunit (CACN4) and the {beta} subunit ({beta}{sub 3}) of VDCCs, both of which are expressed in pancreatic islets, are major components for the VDCC activity, and so they may play a critical role in the regulation of insulin secretion. The authors have determined the structures of the human CACN4 (CACNL1A2) and the human {beta}{sub 3} (CACNLB3) genes. The CACNL1A2 gene spans more than 155 kb and has 49 exons. Most of the positions interrupted by introns are well conserved between the CACNL1A2 gene and the previously reported L-type VDCC {alpha}{sub 1} subunit, CACNL1A1, gene. On the other hand, the CACNLB3 gene distributes in {approximately} 8 kb and comprises 13 exons, most of which are located together within {approximately} 5 kb. Comparisons of the genomic sequences of CACNL1A2 with the previously reported cDNA sequences indicate that there are a number of polymorphisms in the human CACNL1A2 gene. In addition, the PCR-SSCP procedure of exon 1 of CACNL1A2 revealed a change from 7 to 8 ATG trinucleotide repeats in a patient with noninsulin-dependent diabetes mellitus (NIDDM), resulting in an addition of methionine at the amino-terminus of CACN4. The determination of the structures of the human CACNL1A2 and CACNLB3 genes should facilitate study of the role of these genes in the development of NIDDM and also other genetic diseases such as long QT syndrome. 39 refs., 3 figs., 3 tabs.

  14. Understanding calcium dynamics experiments and theory

    CERN Document Server

    Malchow, Dieter

    2003-01-01

    Intracellular Calcium is an important messenger in living cells. Calcium dynamics display complex temporal and spatial structures created by the concentration patterns which are characteristic for a nonlinear system operating far from thermodynamic equilibrium. Written as a set of tutorial reviews on both experimental facts and theoretical modelling, this volume is intended as an introduction and modern reference in the field for graduate students and researchers in biophysics, biochemistry and applied mathematics.

  15. Synthesis and characterization of porous calcium phosphate

    International Nuclear Information System (INIS)

    Granados C, F.; Serrano G, J.; Bonifacio M, J.

    2007-01-01

    The porous calcium phosphate was prepared by the continuous precipitation method using Ca(NO 3 ) 2 .4H 2 O and NH 4 H 2 PO 4 salts. The synthesized material was structurally and superficially characterized using the XRD, BET, IR TGA and SEM techniques. The obtained inorganic material was identified as calcium phosphate that presents a great specific area for what can be efficiently used as adsorbent material for adsorption studies in the radioactive wastes treatment present in aqueous solution. (Author)

  16. Self-Setting Calcium Orthophosphate Formulations

    Science.gov (United States)

    Dorozhkin, Sergey V.

    2013-01-01

    In early 1980s, researchers discovered self-setting calcium orthophosphate cements, which are bioactive and biodegradable grafting bioceramics in the form of a powder and a liquid. After mixing, both phases form pastes, which set and harden forming either a non-stoichiometric calcium deficient hydroxyapatite or brushite. Since both of them are remarkably biocompartible, bioresorbable and osteoconductive, self-setting calcium orthophosphate formulations appear to be promising bioceramics for bone grafting. Furthermore, such formulations possess excellent molding capabilities, easy manipulation and nearly perfect adaptation to the complex shapes of bone defects, followed by gradual bioresorption and new bone formation. In addition, reinforced formulations have been introduced, which might be described as calcium orthophosphate concretes. The discovery of self-setting properties opened up a new era in the medical application of calcium orthophosphates and many commercial trademarks have been introduced as a result. Currently such formulations are widely used as synthetic bone grafts, with several advantages, such as pourability and injectability. Moreover, their low-temperature setting reactions and intrinsic porosity allow loading by drugs, biomolecules and even cells for tissue engineering purposes. In this review, an insight into the self-setting calcium orthophosphate formulations, as excellent bioceramics suitable for both dental and bone grafting applications, has been provided. PMID:24956191

  17. Calcium homeostasis in low and high calcium water acclimatized Oreochromis mossambicus exposed to ambient and dietary cadmium

    NARCIS (Netherlands)

    Pratap, H.B.; Wendelaar Bonga, S.E.

    2007-01-01

    The effects of cadmium administered via ambient water (10 mg/l) or food (10 mgCd/fish/day) on plasma calcium, corpuscles of Stannius and bony tissues of Oreochromis mossambicus acclimated to low calcium (0.2 mM) and high calcium (0.8 mM) water were studied for 2, 4, 14 and 35 days. In low calcium

  18. Oral calcium carbonate affects calcium but not phosphorus balance in stage 3-4 chronic kidney disease.

    Science.gov (United States)

    Hill, Kathleen M; Martin, Berdine R; Wastney, Meryl E; McCabe, George P; Moe, Sharon M; Weaver, Connie M; Peacock, Munro

    2013-05-01

    Patients with chronic kidney disease (CKD) are given calcium carbonate to bind dietary phosphorus, reduce phosphorus retention, and prevent negative calcium balance; however, data are limited on calcium and phosphorus balance during CKD to support this. Here, we studied eight patients with stage 3 or 4 CKD (mean estimated glomerular filtration rate 36 ml/min) who received a controlled diet with or without a calcium carbonate supplement (1500 mg/day calcium) during two 3-week balance periods in a randomized placebo-controlled cross-over design. All feces and urine were collected during weeks 2 and 3 of each balance period and fasting blood, and urine was collected at baseline and at the end of each week. Calcium kinetics were determined using oral and intravenous (45)calcium. Patients were found to be in neutral calcium and phosphorus balance while on the placebo. Calcium carbonate supplementation produced positive calcium balance, did not affect phosphorus balance, and produced only a modest reduction in urine phosphorus excretion compared with placebo. Calcium kinetics demonstrated positive net bone balance but less than overall calcium balance, suggesting soft-tissue deposition. Fasting blood and urine biochemistries of calcium and phosphate homeostasis were unaffected by calcium carbonate. Thus, the positive calcium balance produced by calcium carbonate treatment within 3 weeks cautions against its use as a phosphate binder in patients with stage 3 or 4 CKD, if these findings can be extrapolated to long-term therapy.

  19. Factors to consider in the selection of a calcium supplement.

    OpenAIRE

    Shangraw, R F

    1989-01-01

    Calcium supplements are widely used, yet many questions remain as to the absorption of various calcium salts. Because the solubility of many calcium salts is dependent upon pH, the type of salt used, the condition of the patient, and the time of administration should be considered. Studies show that many calcium supplements on the market today do not meet standards of quality established in the "U.S. Pharmacopeia" (USP). Consumers must be discerning about the products they purchase. Calcium s...

  20. Estimation of ionized calcium, total calcium and albumin corrected calcium for the diagnosis of hypocalcaemia of malignancy

    International Nuclear Information System (INIS)

    Ijaz, A.; Mehmood, T.; Qureshi, A.H.; Anwar, M.; Dilawar, M.; Hussain, I.; Khan, F.A.; Khan, D.A.; Hussain, S.; Khan, I.A.

    2006-01-01

    Objective: To measure levels of ionized calcium, total calcium and albumin corrected calcium in patients with different malignant disorders for the diagnosis of hypercalcaemia of malignancy. Design: A case control comparative study. Place and Duration of Study: The study was carried out in the Department of Pathology, Army Medical College Rawalpindi, Armed Forces Institute of Pathology and Department of Oncology CMH, Rawalpindi from March 2003 to December 2003. Subjects and Methods: Ninety-seven patients of various malignant disorders, admitted in the Department of Oncology, CMH, Rawalpindi, and 39 age and gender-matched disease-free persons (as control) were included in the study. Blood ionized calcium (Ca/sup ++/), pH, sodium (Na/sup +/) and potassium (K/sup +/) were analysed by Ion selective electrode (ISE) on Easylyte> auto analyser. Other related parameters were measured by colorimetric methods. Results: Blood Ca/sup ++/ levels in patients suffering from malignant disorders were found significantly high (mean +- j 1.30+017 mmoV/L) as compared to control subjects (mean +- 1.23+0.03 mmoV/L) (p<0.001). The number of patients with hypercalcaemia of malignancy detected by Ca/sup ++/ estimation was significantly higher (38%) as compared to total calcium (8.4%) and albumin corrected calcium ACC (10.6%) (p<0.001). There was no statistically significant difference in other parameters e.g. phosphate, urea, creatinine, pH, Na/sup +/ and K/sup +/ levels in study subjects and controls. Conclusion: Detection of hypercalcaemia can be markedly improved if ionized calcium estimation is used in patients with malignant disorders. (author)

  1. Expanding the neuron's calcium signaling repertoire: intracellular calcium release via voltage-induced PLC and IP3R activation.

    Directory of Open Access Journals (Sweden)

    Stefanie Ryglewski

    2007-04-01

    Full Text Available Neuronal calcium acts as a charge carrier during information processing and as a ubiquitous intracellular messenger. Calcium signals are fundamental to numerous aspects of neuronal development and plasticity. Specific and independent regulation of these vital cellular processes is achieved by a rich bouquet of different calcium signaling mechanisms within the neuron, which either can operate independently or may act in concert. This study demonstrates the existence of a novel calcium signaling mechanism by simultaneous patch clamping and calcium imaging from acutely isolated central neurons. These neurons possess a membrane voltage sensor that, independent of calcium influx, causes G-protein activation, which subsequently leads to calcium release from intracellular stores via phospholipase C and inositol 1,4,5-trisphosphate receptor activation. This allows neurons to monitor activity by intracellular calcium release without relying on calcium as the input signal and opens up new insights into intracellular signaling, developmental regulation, and information processing in neuronal compartments lacking calcium channels.

  2. Heterogeneity of trans-callosal structural connectivity and effects on resting state subnetwork integrity may underlie both wanted and unwanted effects of therapeutic corpus callostomy

    Directory of Open Access Journals (Sweden)

    Peter Neal Taylor

    2016-01-01

    Conclusion: Consideration of the selective vulnerability of resting state sub-networks, and of between-individual variability in connectivity patterns, sheds new light on the occurrence of both wanted and unwanted effects of callosotomy. We propose that beneficial effects (seizure reduction relate to disruption of the default mode network, with unwanted “disconnection syndrome” effects due to disruption particularly of the somatomotor and frontoparietal RSNs. Our results may also explain why disconnection syndromes primary reflect lateralised sensory-motor problems (e.g. of limb movement rather than midline function (e.g. tongue movement. Marked between-subject variation in callosal connectivity may underlie the poor predictability of effects of callosotomy. High resolution structural connectivity studies of this nature may be useful in pre-surgical planning of therapeutic callosotomy for intractable epilepsy.

  3. What factors underlie children's susceptibility to semantic and phonological false memories? investigating the roles of language skills and auditory short-term memory.

    Science.gov (United States)

    McGeown, Sarah P; Gray, Eleanor A; Robinson, Jamey L; Dewhurst, Stephen A

    2014-06-01

    Two experiments investigated the cognitive skills that underlie children's susceptibility to semantic and phonological false memories in the Deese/Roediger-McDermott procedure (Deese, 1959; Roediger & McDermott, 1995). In Experiment 1, performance on the Verbal Similarities subtest of the British Ability Scales (BAS) II (Elliott, Smith, & McCulloch, 1997) predicted correct and false recall of semantic lures. In Experiment 2, performance on the Yopp-Singer Test of Phonemic Segmentation (Yopp, 1988) did not predict correct recall, but inversely predicted the false recall of phonological lures. Auditory short-term memory was a negative predictor of false recall in Experiment 1, but not in Experiment 2. The findings are discussed in terms of the formation of gist and verbatim traces as proposed by fuzzy trace theory (Reyna & Brainerd, 1998) and the increasing automaticity of associations as proposed by associative activation theory (Howe, Wimmer, Gagnon, & Plumpton, 2009). Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Effect of postnatal development on calcium currents and slow charge movement in mammalian skeletal muscle.

    Science.gov (United States)

    Beam, K G; Knudson, C M

    1988-06-01

    Single- (whole-cell patch) and two-electrode voltage-clamp techniques were used to measure transient (Ifast) and sustained (Islow) calcium currents, linear capacitance, and slow, voltage-dependent charge movements in freshly dissociated fibers of the flexor digitorum brevis (FDB) muscle of rats of various postnatal ages. Peak Ifast was largest in FDB fibers of neonatal (1-5 d) rats, having a magnitude in 10 mM external Ca of 1.4 +/- 0.9 pA/pF (mean +/- SD; current normalized by linear fiber capacitance). Peak Ifast was smaller in FDB fibers of older animals, and by approximately 3 wk postnatal, it was so small as to be unmeasurable. By contrast, the magnitudes of Islow and charge movement increased substantially during postnatal development. Peak Islow was 3.6 +/- 2.5 pA/pF in FDB fibers of 1-5-d rats and increased to 16.4 +/- 6.5 pA/pF in 45-50-d-old rats; for these same two age groups, Qmax, the total mobile charge measurable as charge movement, was 6.0 +/- 1.7 and 23.8 +/- 4.0 nC/microF, respectively. As both Islow and charge movement are thought to arise in the transverse-tubular system, linear capacitance normalized by the area of fiber surface was determined as an indirect measure of the membrane area of the t-system relative to that of the fiber surface. This parameter increased from 1.5 +/- 0.2 microF/cm2 in 2-d fibers to 2.9 +/- 0.4 microF/cm2 in 44-d fibers. The increases in peak Islow, Qmax, and normalized linear capacitance all had similar time courses. Although the function of Islow is unknown, the substantial postnatal increase in its magnitude suggests that it plays an important role in the physiology of skeletal muscle.

  5. Disease Stage-Dependent Changes in Cardiac Contractile Performance and Oxygen Utilization Underlie Reduced Myocardial Efficiency in Human Inherited Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Güçlü, Ahmet; Knaapen, Paul; Harms, Hendrik J; Parbhudayal, Rahana Y; Michels, Michelle; Lammertsma, Adriaan A; van Rossum, Albert C; Germans, Tjeerd; van der Velden, Jolanda

    2017-05-01

    Reduced myocardial efficiency represents a target for therapy in hypertrophic cardiomyopathy although therapeutic benefit may depend on disease stage. Here, we determined disease stage-dependent changes in myocardial efficiency and effects of myectomy surgery. Myocardial external efficiency (MEE) was determined in 27 asymptomatic mutation carriers (genotype positive/phenotype negative), 10 patients with hypertrophic obstructive cardiomyopathy (HOCM), 10 patients with aortic valve stenosis, and 14 healthy individuals using [ 11 C]-acetate positron emission tomography and cardiovascular magnetic resonance imaging. Follow-up measurements were performed in HOCM and aortic valve stenosis patients 4 months after surgery. External work did not differ in HOCM compared with controls, whereas myocardial oxygen consumption was lower in HOCM. Because of a higher cardiac mass, total cardiac oxygen consumption was significantly higher in HOCM than in controls and genotype positive/phenotype negative. MEE was significantly lower in genotype positive/phenotype negative than in controls (28±6% versus 42±6%) and was further decreased in HOCM (22±5%). In contrast to patients with aortic valve stenosis, MEE was not improved in patients with HOCM after surgery, which was explained by opposite changes in the septum (decrease) and lateral (increase) wall. Different mechanisms underlie reduced MEE at the early and advanced stage of hypertrophic cardiomyopathy. The initial increase and subsequent reduction in myocardial oxygen consumption during disease progression indicates that energy deficiency is a primary mutation-related event, whereas mechanisms secondary to disease remodeling underlie low MEE in HOCM. Our data highlight that the benefit of therapies to improve energetic status of the heart may vary depending on the disease stage and that treatment should be initiated before cardiac remodeling. © 2017 American Heart Association, Inc.

  6. CDKN2A/B Deletion and Double-hit Mutations of the MAPK Pathway Underlie the Aggressive Behavior of Langerhans Cell Tumors.

    Science.gov (United States)

    Xerri, Luc; Adélaïde, José; Popovici, Cornel; Garnier, Séverine; Guille, Arnaud; Mescam-Mancini, Lenaïg; Laurent, Camille; Brousset, Pierre; Coze, Carole; Michel, Gérard; Chaffanet, Max; Bouabdallah, Reda; Coso, Diane; Bertucci, François; Birnbaum, Daniel

    2018-02-01

    Langerhans cell histiocytosis (LCH) has a mostly favorable outcome, whereas Langerhans cell sarcoma (LCS) is an aggressive tumor. It is still unclear whether any specific molecular alterations could underlie the aggressive behavior of Langerhans cell proliferations. We used targeted next-generation sequencing and array-comparative genomic hybridization to profile 22 LCH samples from different patients together with 3 LCS samples corresponding to different relapses from the same patient. The third LCS relapse was a composite tumor including both B-cell chronic lymphocytic leukemia and LCS components. The 22 LCH samples were mostly of bone origin and showed classic histophenotypical features. Array-comparative genomic hybridization showed in all 3 LCS samples a similar homozygous somatic loss affecting the CDKN2A/B locus, whereas the 17 informative LCH samples did not show any detectable abnormality. In the 3 LCS samples, targeted next-generation sequencing of 495 cancer genes detected common mutations in KMT2D/MLL2 and in both MAP2K1 and NRAS genes, whereas BRAF was not mutated. A NOTCH1 mutation was acquired in 2 LCS samples. The composite LCS/B-cell chronic lymphocytic leukemia tumor showed the same genetic profile in its 2 components. LCH samples showed mutually exclusive mutations of BRAF (8/20) and MAP2K1 (4/19), but no mutation of KMT2D, NRAS nor NOTCH1. These results suggest that CDKN2A/B deletion and/or simultaneous mutations of MAP2K1 and NRAS may underlie the aggressive behavior of Langerhans cell tumors, and thus could be useful for the diagnosis of malignancy in histiocytic neoplasms. The MAPK pathway "double hit" profile provides a basis for targeted therapy in LCS patients.

  7. Structure-activity relationship study and discovery of indazole 3-carboxamides as calcium-release activated calcium channel blockers

    OpenAIRE

    Bai, Sha; Nagai, Masazumi; Koerner, Steffi K.; Veves, Aristidis; Sun, Lijun

    2016-01-01

    Aberrant activation of mast cells contributes to the development of numerous diseases including cancer, autoimmune disorders, as well as diabetes and its complications. The influx of extracellular calcium via the highly calcium selective calcium-release activated calcium (CRAC) channel controls mast cell functions. Intracellular calcium homeostasis in mast cells can be maintained via the modulation of the CRAC channel, representing a critical point for therapeutic interventions. We describe t...

  8. Calcium response to vitamin D supplementation

    Directory of Open Access Journals (Sweden)

    Francisco R. Spivacow

    2018-01-01

    Full Text Available Several studies show the importance of serum vitamin D sufficient levels to prevent multiple chronic diseases. However, vitamin D supplementation and its effects on urine calcium excretion remain controversial. The objective of this prospective and interventional study was to evaluate urine calcium excretion in women with normal calciuria or hypercalciuria, once serum vitamin D sufficiency was achieved. We studied 63 women with idiopathic hypercalciuria, (9 with renal lithiasis and 50 normocalciuric women. Both groups had serum vitamin D levels low (deficiency or insufficiency. Baseline urine calcium excretion was measured before being supplemented with vitamin D2 or D3 weekly or vitamin D3 100.000 IU monthly. Once serum vitamin D levels were corrected achieving at least 30 ng/ml, a second urine calcium excretion was obtained. Although in the whole sample we did not observe significant changes in urine calcium excretion according to the way of supplementation, some of those with weekly supplementation had significant higher urine calcium excretion, 19% (n = 12 of hypercalciuric women and 12% (n = 6 of the normocalciuric group. Monthly doses, also showed higher urine calcium excretion in 40% of hypercalciuric women (n = 4/10 and in 44% (n = 4/9 of the renal lithiasis hypercalciuric patients. In conclusion, different ways of vitamin D supplementation and adequate serum levels are safe in most patients, although it should be taken into account a subgroup, mainly with monthly loading doses, that could increase the calciuria significantly eventually rising renal lithiasis risk or bone mass loss, if genetically predisposed.

  9. Calcium soap from palm fatty acid distillate (PFAD for ruminant feed: quality of calcium source

    Directory of Open Access Journals (Sweden)

    Handojo Lienda A.

    2018-01-01

    Full Text Available Calcium soap is potentially used as fat supplements for ruminants since it contains high concentration of fat and calcium that are useful for ruminants. The consumption of calcium soap may increase the yield and the fat content of milk, as well as increase the ruminant’s fertility. Calcium soap can be produced from palm fatty acid distillate (PFAD, which is a by-product of crude palm oil (CPO refining process, and calcium oxide (CaO. In this study, the effect of CaO quality on the acid value of the product has been observed. It was found that the reaction with lower concentration of active calcium of CaO resulted in products with a higher acid value, which indicates a lower reaction conversion. Thus, the produced calcium soap requires further treatment in order to remove the unreacted calcium and free fatty acid. Washing with hexane followed by either vacuum or convection drying has been found to be able to reduce the acid value of the product significantly.

  10. Eggshell powder, a comparable or better source of calcium than purified calcium carbonate: Piglet studies

    NARCIS (Netherlands)

    Schaafsma, A.; Beelen, G.M.

    1999-01-01

    Powdered chicken eggshells might be an interesting and widely available source of calcium. In two studies using piglets we determined the digestibility of calcium from different diets. The first study compared casein-based diets with CaCO3 (CasCC) or eggshell powder (CasES). The second study

  11. Relative biological activity of amorphous calcium and calcium-magnesium phosphates

    International Nuclear Information System (INIS)

    Silina, E.N.; Kunitsa, T.N.; Shuslikova, E.S.; Griggs, J.; Levchenko, L.V.; Karjaubaeva, R.A.; Sinyayev, V.A.

    2005-01-01

    Three amorphous calcium and calcium-magnesium phosphates that are close on composition to mineral basis of the bone tissues are compared on bioactivity in the given article. Properties of the hydrated substances produced from water solutions and their derivations, which are formed due to thermal treatment, are discussed here. As a detector of bioactivity was used microbial culture E-Coli. [author

  12. Calcium spikes and calcium plateaux evoked by differential polarization in dendrites of turtle motoneurones in vitro

    DEFF Research Database (Denmark)

    Hounsgaard, J; Kiehn, O

    1993-01-01

    The ability of dendrites in turtle motoneurones to support calcium spikes and calcium plateaux was investigated using differential polarization by applied electric fields. 2. Electric fields were generated by passing current through transverse slices of the turtle spinal cord between two plate......+ spikes and Ca2+ plateaux are present in dendrites of spinal motoneurones of the turtle....

  13. Derivation of a formula for adjusting the total serum calcium in ...

    African Journals Online (AJOL)

    GRACE

    2006-06-16

    Jun 16, 2006 ... homeostasis. Calcium sensing receptors have also been identified. The total serum calcium is accounted for as calcium bound to protein, ionized calcium and calcium complexed to citrate, lactate, sulphate, carbonate and phosphate. The calcium bound to protein and ionized calcium is roughly in equal ...

  14. Effect of dietary calcium and phosphorus on intestinal calcium absorption and vitamin D metabolism

    International Nuclear Information System (INIS)

    Ribovich, M.L.; DeLuca, H.F.

    1978-01-01

    To understand better dietary regulation of intestinal calcium absorption, a quantitative assessment of the metabolites in plasma and duodenum of rats given daily doses of radioactive vitamin D 3 and diets differing in calcium and phosphorus content was made. All known vitamin D metabolites were ultimately identified by high-pressure liquid chromatography. In addition to the known metabolites (25-hydroxyvitamin D 3 , 24,25-dihydroxyvitamin D 3 , 1,25-dihydroxyvitamin D 3 , 25,26-dihydroxyvitamin D 3 , and 1,24,25-trihydroxyvitamin D 3 ), several new and unidentified metabolites were found. In addition to 1,25-dihydroxyvitamin D 3 and 1,24,25-trihydroxyvitamin D 3 , the levels of some of the unknown metabolites could be correlated with intestinal calcium transport. However, whether or not any of these metabolites plays a role in the stimulation of intestinal calcium absorption by low dietary calcium or low dietary phosphorus remains unknown

  15. Calcium carbonate scaling kinetics determined from radiotracer experiments with calcium-47

    International Nuclear Information System (INIS)

    Turner, C.W.; Smith, D.W.

    1998-01-01

    The deposition rate of calcium carbonate on a heat-transfer surface has been measured using a calcium-47 radiotracer and compared to the measured rate of thermal fouling. The crystalline phase of calcium carbonate that precipitates depends on the degree of supersaturation at the heat-transfer surface, with aragonite precipitating at higher supersaturations and calcite precipitating at lower supersaturations. Whereas the mass deposition rates were constant with time, the thermal fouling rates decreased throughout the course of each experiment as a result of densification of the deposit. It is proposed that the densification was driven by the temperature gradient across the deposit together with the retrograde solubility of calcium carbonate. The temperature dependence of the deposition rate yielded an activation energy of 79 ± 4 kJ/mol for the precipitation of calcium carbonate on a heat-transfer surface. (author)

  16. Discovery and Development of Calcium Channel Blockers

    Science.gov (United States)

    Godfraind, Théophile

    2017-01-01

    In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovered by Sidney Ringer who reported this fact in 1883. Interest in the intracellular role of calcium arose 60 years later out of Kamada (Japan) and Heibrunn (USA) experiments in the early 1940s. Studies on pharmacology of calcium function were initiated in the mid 1960s and their therapeutic applications globally occurred in the the 1980s. The first part of this report deals with basic pharmacology in the cardiovascular system particularly in isolated arteries. In the section entitled from calcium antagonists to calcium channel blockers, it is recalled that drugs of a series of diphenylpiperazines screened in vivo on coronary bed precontracted by angiotensin were initially named calcium antagonists on the basis of their effect in depolarized arteries contracted by calcium. Studies on arteries contracted by catecholamines showed that the vasorelaxation resulted from blockade of calcium entry. Radiochemical and electrophysiological studies performed with dihydropyridines allowed their cellular targets to be identified with L-type voltage-operated calcium channels. The modulated receptor theory helped the understanding of their variation in affinity dependent on arterial cell membrane potential and promoted the terminology calcium channel blocker (CCB) of which the various chemical families are introduced in the paper. In the section entitled tissue selectivity of CCBs, it is shown that characteristics of the drug, properties of the tissue, and of the stimuli are important factors of

  17. Discovery and Development of Calcium Channel Blockers.

    Science.gov (United States)

    Godfraind, Théophile

    2017-01-01

    In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovered by Sidney Ringer who reported this fact in 1883. Interest in the intracellular role of calcium arose 60 years later out of Kamada (Japan) and Heibrunn (USA) experiments in the early 1940s. Studies on pharmacology of calcium function were initiated in the mid 1960s and their therapeutic applications globally occurred in the the 1980s. The first part of this report deals with basic pharmacology in the cardiovascular system particularly in isolated arteries. In the section entitled from calcium antagonists to calcium channel blockers, it is recalled that drugs of a series of diphenylpiperazines screened in vivo on coronary bed precontracted by angiotensin were initially named calcium antagonists on the basis of their effect in depolarized arteries contracted by calcium. Studies on arteries contracted by catecholamines showed that the vasorelaxation resulted from blockade of calcium entry. Radiochemical and electrophysiological studies performed with dihydropyridines allowed their cellular targets to be identified with L-type voltage-operated calcium channels. The modulated receptor theory helped the understanding of their variation in affinity dependent on arterial cell membrane potential and promoted the terminology calcium channel blocker (CCB) of which the various chemical families are introduced in the paper. In the section entitled tissue selectivity of CCBs, it is shown that characteristics of the drug, properties of the tissue, and of the stimuli are important factors of

  18. Discovery and Development of Calcium Channel Blockers

    Directory of Open Access Journals (Sweden)

    Théophile Godfraind

    2017-05-01

    Full Text Available In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovered by Sidney Ringer who reported this fact in 1883. Interest in the intracellular role of calcium arose 60 years later out of Kamada (Japan and Heibrunn (USA experiments in the early 1940s. Studies on pharmacology of calcium function were initiated in the mid 1960s and their therapeutic applications globally occurred in the the 1980s. The first part of this report deals with basic pharmacology in the cardiovascular system particularly in isolated arteries. In the section entitled from calcium antagonists to calcium channel blockers, it is recalled that drugs of a series of diphenylpiperazines screened in vivo on coronary bed precontracted by angiotensin were initially named calcium antagonists on the basis of their effect in depolarized arteries contracted by calcium. Studies on arteries contracted by catecholamines showed that the vasorelaxation resulted from blockade of calcium entry. Radiochemical and electrophysiological studies performed with dihydropyridines allowed their cellular targets to be identified with L-type voltage-operated calcium channels. The modulated receptor theory helped the understanding of their variation in affinity dependent on arterial cell membrane potential and promoted the terminology calcium channel blocker (CCB of which the various chemical families are introduced in the paper. In the section entitled tissue selectivity of CCBs, it is shown that characteristics of the drug, properties of the tissue, and of the stimuli are

  19. Calcium-Induced calcium release during action potential firing in developing inner hair cells.

    Science.gov (United States)

    Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J

    2015-03-10

    In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights

  20. Bioavailability of vitamin D₂ and calcium from fortified milk.

    Science.gov (United States)

    Kaushik, Ravinder; Sachdeva, Bhawana; Arora, Sumit; Kapila, Suman; Wadhwa, Balbir Kaur

    2014-03-15

    The objective of the present investigation was to determine bioavailability of calcium and vitamin D₂ from milk fortified with either calcium or vitamin D₂ alone or when both were used for preparation of multiple micronutrient fortified milk and also to study its interaction with iron and zinc bioavailability. 32 weanling male rats (aged 21-28 days) were assigned into four groups and were fed milk and milk fortified with calcium, vitamin D₂ and calcium+vitamin D₂. Vitamin D₂ increased calcium bioavailability. In multiple micronutrient fortified milk, the bioavailability of both calcium+vitamin D₂ increased in comparison to single fortification. Calcium fortification decreased, whereas vitamin D₂ increased the absorption of iron and zinc. However, calcium and vitamin D₂ when fortified in combination, the iron and zinc bioavailability was similar to control group. There was positive association between bioavailability of calcium and vitamin D₂. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Localization of calcium changes in stimulated rat mast cells.

    Science.gov (United States)

    Horoyan, M; Soler, M; Benoliel, A M; Fraterno, M; Passerel, M; Subra, H; Martin, J M; Bongrand, P; Foa, C

    1992-01-01

    We studied intracellular free, bound, and sequestered calcium in rat mast cells after various stimulations. The use of a fluorescent probe combined with digitized imaging on individual living cells demonstrated transient increases of free Ca2+ in the micromolar range. The use of histochemical techniques (K pyroantimonate and anhydrous fixation), together with X-ray microanalysis, energy electron-loss spectroscopy, and electron spectroscopic imaging, revealed large amounts of stored calcium within the cells (in the millimolar range). Chelation experiments and stimulations enabled us to identify at least two pools of bound calcium which exhibited different dynamic behaviors. Stimulation in the presence of EGTA did not modify calcium from granules, granule membranes, and heterochromatin, whereas it decreased calcium from other cell compartments. Stimulation triggered variations in the amount of bound calcium but they did not parallel free calcium movements. Hence, whereas free calcium is implicated in exocytosis, bound calcium may be involved in altogether different cell functions.

  2. Absorption of levothyroxine when coadministered with various calcium formulations.

    Science.gov (United States)

    Zamfirescu, Isabelle; Carlson, Harold E

    2011-05-01

    Calcium carbonate is a commonly used dietary supplement and has been shown to interfere with levothyroxine absorption. However, calcium citrate, which is also used for supplementation purposes, has not been studied previously and calcium acetate, which is used to treat hyperphosphatemia in renal failure, has been reported to show little or no interference with levothyroxine absorption in a retrospective pharmacoepidemiologic study. We aimed to compare the effect of these three calcium formulations on levothyroxine absorption. The study was conducted in eight healthy, euthyroid adults. We performed single-dose pharmacokinetic studies in which we measured levothyroxine absorption when given alone or when coadministered with calcium carbonate, calcium citrate, or calcium acetate in doses containing 500 mg elemental calcium. Serum thyroxine was measured at intervals over a 6-hour period after ingestion of the study drugs. Coadministration of each of the three calcium preparations significantly reduced levothyroxine absorption by about 20%-25% compared with levothyroxine given alone. Contrary to a prior report, our data suggest that calcium acetate interferes with levothyroxine absorption in a manner similar to that seen with calcium carbonate and calcium citrate. Although the effect of calcium is modest compared with some other medications previously studied, hypothyroid patients should be cautioned to take their levothyroxine well-separated from all of these calcium formulations.

  3. Contracture of Slow Striated Muscle during Calcium Deprivation

    Science.gov (United States)

    Irwin, Richard L.; Hein, Manfred M.

    1963-01-01

    When deprived of calcium the slow striated muscle fibers of the frog develop reversible contractures in either hypertonic or isotonic solutions. While calcium deprivation continues because of a flowing calcium-free solution the muscles relax slowly and completely. Restoration of calcium during contracture relaxes the muscle promptly to initial tension. When relaxed during calcium lack the return of calcium does not change tension and the muscle stays relaxed. When contractures are induced by solutions containing small amounts of calcium relaxation does not occur or requires several hours. The rate of tension development depends upon the rate at which calcium moves outward since the contractures develop slower in low concentrations of calcium and are absent or greatly slowed in a stagnant calcium-free solution. Withdrawal of calcium prevents the contractile responses to ACh, KCl, or electrical stimulation through the nerve. Muscles return to their original excitability after calcium is restored. Origin of the contractures is unrelated to nerve activity since they are maximal during transmission failure from calcium lack, occur in denervated muscles, and are not blocked by high concentrations of d-tubocurarine, procaine, or atropine. The experiments also indicate that the contractures do not originate from repetitive activity of muscle membranes. The findings are most simply explained by relating the outward movement of calcium as a link for initiating contraction in slow type striated muscle. PMID:14065284

  4. The spatial pattern of atrial cardiomyocyte calcium signalling modulates contraction.

    Science.gov (United States)

    Mackenzie, Lauren; Roderick, H Llewelyn; Berridge, Michael J; Conway, Stuart J; Bootman, Martin D

    2004-12-15

    We examined the regulation of calcium signalling in atrial cardiomyocytes during excitation-contraction coupling, and how changes in the distribution of calcium impacts on contractility. Under control conditions, calcium transients originated in subsarcolemmal locations and showed local regeneration through activation of calcium-induced calcium release from ryanodine receptors. Despite functional ryanodine receptors being expressed at regular (approximately 2 microm) intervals throughout atrial myocytes, the subsarcolemmal calcium signal did not spread in a fully regenerative manner through the interior of a cell. Rather, there was a diminishing centripetal propagation of calcium. The lack of regeneration was due to mitochondria and SERCA pumps preventing the inward movement of calcium. Inhibiting these calcium buffering mechanisms allowed the globalisation of action potential-evoked responses. In addition, physiological positive inotropic agents, such as endothelin-1 and beta-adrenergic agonists, as well as enhanced calcium current, calcium store loading and inositol 1,4,5-trisphosphate infusion also led to regenerative global responses. The consequence of globalising calcium signals was a significant increase in cellular contraction. These data indicate how calcium signals and their consequences are determined by the interplay of multiple subcellular calcium management systems.

  5. Role of claudins in renal calcium handling

    Directory of Open Access Journals (Sweden)

    Armando Luis Negri

    2015-07-01

    Full Text Available Paracellular channels occurring in tight junctions play a major role in transepithelial ionic flows. This pathway includes a high number of proteins, such as claudins. Within renal epithelium, claudins result in an ionic selectivity in tight junctions. Ascending thick limb of loop of Henle (ATLH is the most important segment for calcium reabsorption in renal tubules. Its cells create a water-proof barrier, actively transport sodium and chlorine through a transcellular pathway, and provide a paracellular pathway for selective calcium reabsorption. Several studies have led to a model of paracellular channel consisting of various claudins, particularly claudin-16 and 19. Claudin-16 mediates cationic paracellular permeability in ATLH, whereas claudin-19 increases cationic selectivity of claudin-16 by blocking anionic permeability. Recent studies have shown that claudin-14 promoting activity is only located in ATLH. When co-expressed with claudin-16, claudin-14 inhibits the permeability of claudin-16 and reduces paracellular permeability to calcium. Calcium reabsorption process in ATLH is closely regulated by calcium sensor receptor (CaSR, which monitors circulating Ca levels and adjusts renal excretion rate accordingly. Two microRNA, miR-9 and miR-374, are directly regulated by CaSR. Thus, miR-9 and miR-374 suppress mRNA translation for claudin-14 and induce claudin-14 decline.

  6. Calcium and bone disorders in pregnancy

    Directory of Open Access Journals (Sweden)

    Shriraam Mahadevan

    2012-01-01

    Full Text Available Significant transplacental calcium transfer occurs during pregnancy, especially during the last trimester, to meet the demands of the rapidly mineralizing fetal skeleton. Similarly, there is an obligate loss of calcium in the breast milk during lactation. Both these result in considerable stress on the bone mineral homeostasis in the mother. The maternal adaptive mechanisms to conserve calcium are different in pregnancy and lactation. During pregnancy, increased intestinal absorption of calcium from the gut mainly due to higher generation of calcitriol (1,25 dihydroxy vitamin D helps in maintaining maternal calcium levels. On the other hand, during lactation, the main compensatory mechanism is skeletal resorption due to increased generation of parathormone related peptide (PTHrP from the breast. Previous studies suggest that in spite of considerable changes in bone mineral metabolism during pregnancy, parity and lactation are not significantly associated with future risk for osteoporosis. However, in India, the situation may not be the same as a significant proportion of pregnancies occur in the early twenties when peak bone mass is not yet achieved. Further, malnutrition, anemia and vitamin D deficiency are commonly encountered in this age group. This may have an impact on future bone health of the mother. It may also probably provide an opportunity for health care providers for prevention. Other metabolic bone diseases like hypoparathyroidism, hyperparathyroidism and pseudohypoparathyroidism are rarely encountered in pregnancy. Their clinical implications and management are also discussed.

  7. Calcium's Role in Mechanotransduction during Muscle Development

    Directory of Open Access Journals (Sweden)

    Tatiana Benavides Damm

    2014-01-01

    Full Text Available Mechanotransduction is a process where cells sense their surroundings and convert the physical forces in their environment into an appropriate response. Calcium plays a crucial role in the translation of such forces to biochemical signals that control various biological processes fundamental in muscle development. The mechanical stimulation of muscle cells may for example result from stretch, electric and magnetic stimulation, shear stress, and altered gravity exposure. The response, mainly involving changes in intracellular calcium concentration then leads to a cascade of events by the activation of downstream signaling pathways. The key calcium-dependent pathways described here include the nuclear factor of activated T cells (NFAT and mitogen-activated protein kinase (MAPK activation. The subsequent effects in cellular homeostasis consist of cytoskeletal remodeling, cell cycle progression, growth, differentiation, and apoptosis, all necessary for healthy muscle development, repair, and regeneration. A deregulation from the normal process due to disuse, trauma, or disease can result in a clinical condition such as muscle atrophy, which entails a significant loss of muscle mass. In order to develop therapies against such diseased states, we need to better understand the relevance of calcium signaling and the downstream responses to mechanical forces in skeletal muscle. The purpose of this review is to discuss in detail how diverse mechanical stimuli cause changes in calcium homeostasis by affecting membrane channels and the intracellular stores, which in turn regulate multiple pathways that impart these effects and control the fate of muscle tissue.

  8. Role of claudins in renal calcium handling.

    Science.gov (United States)

    Negri, Armando Luis

    2015-01-01

    Paracellular channels occurring in tight junctions play a major role in transepithelial ionic flows. This pathway includes a high number of proteins, such as claudins. Within renal epithelium, claudins result in an ionic selectivity in tight junctions. Ascending thick limb of loop of Henle (ATLH) is the most important segment for calcium reabsorption in renal tubules. Its cells create a water-proof barrier, actively transport sodium and chlorine through a transcellular pathway, and provide a paracellular pathway for selective calcium reabsorption. Several studies have led to a model of paracellular channel consisting of various claudins, particularly claudin-16 and 19. Claudin-16 mediates cationic paracellular permeability in ATLH, whereas claudin-19 increases cationic selectivity of claudin-16 by blocking anionic permeability. Recent studies have shown that claudin-14 promoting activity is only located in ATLH. When co-expressed with claudin-16, claudin-14 inhibits the permeability of claudin-16 and reduces paracellular permeability to calcium. Calcium reabsorption process in ATLH is closely regulated by calcium sensor receptor (CaSR), which monitors circulating Ca levels and adjusts renal excretion rate accordingly. Two microRNA, miR-9 and miR-374, are directly regulated by CaSR. Thus, miR-9 and miR-374 suppress mRNA translation for claudin-14 and induce claudin-14 decline. Copyright © 2015 The Author. Published by Elsevier España, S.L.U. All rights reserved.

  9. Coronary dilation with nitrocompounds and calcium antagonists.

    Science.gov (United States)

    Jost, S; Rafflenbeul, W; Lichtlen, P R

    1990-01-01

    The vasodilatory effects of nitrocompounds and calcium antagonists on epicardial coronary arteries represent substantial antianginal mechanisms in the presence of coronary vasospasm or eccentric coronary stenoses. With high doses of nitrocompounds, angiographically normal coronary segments can be dilated by an average of approx. 30%, some coronary stenoses even by up to 100%, usually without severe reduction of blood pressure. With calcium antagonists, a similar extent of dilation of normal coronary arteries and eccentric stenoses can be obtained. Our own group demonstrated an average dilation of normal coronary arteries of about 20% after intravenous administration of dihydropyridine calcium antagonists; however, the average systolic blood pressure dropped below 100 mmHg after these compounds. Hence, although in isolated human coronary arteries high concentrations of calcium antagonists were shown to induce a considerably greater vasodilation than nitrocompounds, the early drop in blood pressure prohibits a higher dosage of calcium antagonists in vivo. In the presence of coronary artery disease, particularly when associated with coronary vasospasm, a combination of the two groups of compounds might be recommendable, since an addition of the effects of coronary vasomotor tone is likely. Furthermore, the antianginal effects of a reduction of preload and afterload are complementary.

  10. Transfected parvalbumin alters calcium homeostasis in teratocarcinoma PCC7 cells

    DEFF Research Database (Denmark)

    Müller, B K; Kabos, P; Belhage, B

    1996-01-01

    Indirect evidence supports a protective role of some EF-hand calcium-binding proteins against calcium-induced neurotoxicity. Little is known about how these proteins influence cytosolic calcium levels. After cloning the parvalbumin cDNA into an expression vector, teratocarcinoma cells (PCC7) were...... transfected. Parvalbumin-transfected and mock-transfected cells were loaded with the calcium indicator fura-2 and were exposed, in the same dish, to different concentrations of the calcium ionophore A23187 or to KCI. The results show that parvalbumin-transfected PCC7 cells had much better calcium buffering...

  11. OSTEOPOROSIS IN CALCIUM PYROPHOSPHATE CRYSTAL DEPOSITION DISEASE

    Directory of Open Access Journals (Sweden)

    S A Vladimirov

    2013-01-01

    Full Text Available Objective: to study the incidence of osteoporosis (OP in patients with calcium pyrophosphate crystal deposition disease (CPCDD. Subjects and methods. Eighty patients with CPCDD were examined. Bone mineral density (BMD of the forearm, lumbar spine, and femoral neck was determined by dual-energy X-ray absorptiometry. Laboratory diagnosis involved determination of the blood levels of C-reactive protein, parathyroid hormone, calcium, magnesium, and phosphorus and the daily urinary excretion of calcium and phosphates. Results. The patients with OP were significantly older than those with normal BMD and osteopenia. Forearm bones were the most common isolated location of OP and osteopenia. Injuries in the history, traumatic fractures, and the intake of diuretics were somewhat more common in the patients diagnosed with OP. The incidence of hyperparathyroidism did not differ significantly in the groups.

  12. Frequency Measurement of Tellurium Lines Near Calcium

    Science.gov (United States)

    Dammalapati, Umakanth; Harada, Ken-ichi; Inoue, Takeshi; Ito, Saki; Kawamura, Hirokazu; Sakamoto, Kosuke; Tanaka, Kazuo; Uchiyama, Aiko; Yoshioka, Risa; Sakemi, Yasuhiro

    2017-12-01

    We report measurement of frequencies of tellurium lines with respect to atomic calcium employing a 423 nm commercial violet laser diode placed in an extended cavity. Doppler-free saturated absorption spectroscopy of molecular tellurium is performed on three lines, which are lower and higher in energy to the calcium 4s2 1S0-4s4p 1P1 transition. The measured frequency difference of 717(13) MHz between the strong absorption line, #1508 in the tellurium atlas and the calcium transition is in agreement within 10% of the values available from literature. Wavenumbers of two new tellurium lines are derived from the measurement. In addition, spectroscopy and laser cooling and trapping of francium (n = 7) on the ns 2S1/2-(n + 1)p 2P3/2 transition and spectroscopy of Te2 lines near francium could be performed employing the 423 nm diode laser.

  13. Manganese interferes with calcium, perturbs ERK signaling, and produces embryos with no skeleton.

    Science.gov (United States)

    Pinsino, Annalisa; Roccheri, Maria Carmela; Costa, Caterina; Matranga, Valeria

    2011-09-01

    Manganese (Mn) has been associated with embryo toxicity as it impairs differentiation of neural and skeletogenic cells in vertebrates. Nevertheless, information on the mechanisms operating at the cellular level remains scant. We took advantage of an amenable embryonic model to investigate the effects of Mn in biomineral formation. Sea urchin (Paracentrotus lividus) embryos were exposed to Mn from fertilization, harvested at different developmental stages, and analyzed for their content in calcium (Ca), expression of skeletogenic genes, localization of germ layer markers, and activation of the extracellular signal-regulated kinase (ERK). By optical and immunofluorescence microscopy, we found that Mn exposure produced embryos with no skeleton, by preventing the deposition of the triradiate calcitic spicules usually produced only by specialized mesoderm cells. On the contrary, ectoderm and endoderm differentiation was not impaired. Endogenous Ca content in whole embryos and its localization in Golgi regions of skeletogenic cells was strongly reduced, as measured by atomic absorption spectrometry and in vivo calcein labeling. Spicule-lacking embryos showed persistent ERK activation by immunocytochemistry and immunoblotting, contrary to the physiological oscillations observed in normal embryos. The expression of the skeletogenic genes, Pl-msp130 and Pl-sm30, was also differentially affected if compared with controls. Here, we showed for the first time the ability of Mn to interfere with Ca uptake and internalization into skeletogenic cells and demonstrate that Ca content regulates ERK activation/inactivation during sea urchin embryo morphogenesis. The use of Mn-exposed sea urchin embryos as a new model to study signaling pathways occurring during skeletogenesis will provide new insights into the mechanisms involved in Mn embryo toxicity and underlie the role of calcium in the biomineralization process in vertebrates.

  14. Incidence and progression of aortic valve calcium in the Multi-ethnic Study of Atherosclerosis (MESA).

    Science.gov (United States)

    Owens, David S; Katz, Ronit; Takasu, Junichiro; Kronmal, Richard; Budoff, Matthew J; O'Brien, Kevin D

    2010-03-01

    Aortic valve calcium (AVC) is common among older adults and shares epidemiologic and histopathologic similarities to atherosclerosis. However, prospective studies have failed to identify meaningful risk associations with incident ("new") AVC or its progression. In the present study, AVC was quantified from serial computed tomographic images from 5,880 participants (aged 45 to 84 years) in the Multi-Ethnic Study of Atherosclerosis, using the Agatston method. Multivariate backward selection modeling was used to identify the risk factors for incident AVC and AVC progression. During a mean follow-up of 2.4 +/- 0.9 years, 210 subjects (4.1%) developed incident AVC. The incidence rate (mean 1.7%/year) increased significantly with age (p AVC included age, male gender, body mass index, current smoking, and the use of lipid-lowering and antihypertensive medications. Among those with AVC at baseline, the median rate of AVC progression was 2 Agatston units/year (interquartile range -21 to 37). The baseline Agatston score was a strong, independent predictor of progression, especially among those with high calcium scores at baseline. In conclusion, in this ethnically diverse, preclinical cohort, the rate of incident AVC increased significantly with age. The incident AVC risk was associated with several traditional cardiovascular risk factors, specifically age, male gender, body mass index, current smoking, and the use of both antihypertensive and lipid-lowering medications. AVC progression risk was associated with male gender and the baseline Agatston score. Additional research is needed to determine whether age- and stage-specific mechanisms underlie the risk of AVC progression. Copyright 2010 Elsevier Inc. All rights reserved.

  15. Urinary calcium excretion in essential hypertension.

    Science.gov (United States)

    Young, E W; Morris, C D; McCarron, D A

    1992-10-01

    Patients with essential hypertension have been reported to have higher levels of urinary calcium excretion (UCaV) than normotensive persons. We tested the hypothesis that the calciuria of hypertension is due to dietary factors and evaluated several alternate mechanisms. UCaV was studied in 15 patients with essential hypertension compared with 16 age- and gender-matched normotensive control subjects. For subjects taking self-selected, free-living diets, the difference in UCaV between normotensive (130 +/- 14 mg/day) and hypertensive subjects (201 +/- 37 mg/day) was not significant (p = 0.1). However, in a controlled diet with moderately restricted sodium intake (88 mEq), urinary calcium excretion was significantly higher (p = 0.02) in the hypertensive than in the normotensive group receiving 400 mg calcium (204 +/- 25 vs 132 +/- 13 mg/day) and 1400 mg calcium (272 +/- 31 vs 187 +/- 25 mg/day). Twenty-four-hour UCaV was directly and significantly correlated with blood pressure (r = 0.63 for standing systolic blood pressure; p UCaV (0.12 +/- 0.11 vs 0.12 +/- 0.07 mg per 100 ml glomerular filtration) and serum ionized calcium level (0.06 +/- 0.08 vs 0.06 +/- 0.02 mmol/L) in normotensive and hypertensive subjects, respectively, suggesting that there was no difference in intestinal calcium absorption between the groups. Fasting UCaV did not differ between the hypertensive (8.9 +/- 4.5 mg per 2 hours) and normotensive groups (10.9 +/- 11.5 mg per 2 hours).(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Evolutionary Diversity of the Mitochondrial Calcium Uniporter

    Science.gov (United States)

    Bick, Alexander G.; Calvo, Sarah E.; Mootha, Vamsi K.

    2012-01-01

    Calcium uptake into mitochondria occurs via a recently identified ion channel called the uniporter. Here, we characterize the phylogenomic distribution of the uniporter’s membrane-spanning pore subunit (MCU) and regulatory partner (MICU1). Homologs of both components tend to co-occur in all major branches of eukaryotic life, but both have been lost along certain protozoan and fungal lineages. Several bacterial genomes also contain putative MCU homologs that may represent prokaryotic calcium channels. The analyses indicate that the uniporter may have been an early feature of mitochondria. PMID:22605770

  17. Calcium Oxalate: A Surface Treatment for Limestone

    Directory of Open Access Journals (Sweden)

    Tody M. Cezar

    1998-05-01

    Full Text Available This paper looks at the artificially induced surface conversion of calcium carbonate to the more durable calcium oxalate. Extensive research is being carried out on wall paintings and marble sculpture at the Opicificio delle Pietre Dure e Laboratori di Restauro in Florence, Encouraged by their work, I have researched the effectiveness of the conversion on English limestones. The treated samples have been compared to untreated samples for appearance, hardness, resistance to acid and alkali, porosity, and durability. The results have been assessed considering ease of use, effectiveness, and the appropriateness of the treatment.

  18. NMR study of hydrated calcium silicates

    International Nuclear Information System (INIS)

    Klur, I.

    1996-01-01

    Radioactive wastes storage methods are developed by the CEA. As cements are important materials as well for hours living radioisotopes than for years living radioisotopes, a better knowledge of this material will allow to anticipate its behaviour and to obtain safer storage methods. The structure of calcium silicates (C-S-H) (main constituent of cements) have then been determined in this thesis by nuclear magnetic resonance. This method has allow to explain in structural terms, the different calcium rates that can be measured in the C-S-H too. (O.M.)

  19. Plasma concentration of ionized calcium in healthy iguanas.

    Science.gov (United States)

    Dennis, P M; Bennett, R A; Harr, K E; Lock, B A

    2001-08-01

    To measure plasma concentration of ionized calcium in healthy green iguanas. Prospective study. 9 juvenile and 21 (10 male, 11 female) adult iguanas. Blood samples were obtained from each iguana, and plasma calcium, glucose, phosphorus, uric acid, total protein, albumin, globulin, potassium, and ionized calcium concentrations, aspartate transaminase (AST) activity, and pH were measured. Heparinized blood was used for measurement of ionized calcium concentration and blood pH. A CBC was also performed to assess the health of the iguanas. Significant differences were not detected among the 3 groups (juveniles, males, and females) with regard to ionized calcium concentration. Mean ionized calcium concentration measured in blood was 1.47 +/- 0.105 mmol/L. Significant differences were detected between juveniles and adults for values of phosphorus, glucose, total protein, albumin, globulin, and AST activity. Ionized calcium concentration provides a clinical measurement of the physiologically active calcium in circulation. Evaluation of physiologically active calcium in animals with suspected calcium imbalance that have total plasma calcium concentrations within reference range or in gravid animals with considerably increased total plasma calcium concentrations is vital for determining a therapeutic plan. Accurate evaluation of calcium status will provide assistance in the diagnosis of renal disease and seizures and allow for better evaluation of the health status of gravid female iguanas.

  20. Avian eggshell formation in calcium-rich and calcium-poor habitats: Importance of snail shells and anthropogenic calcium sources

    NARCIS (Netherlands)

    Graveland, J.

    1996-01-01

    Most passerines depend on the intake of calcium-rich material in addition to their normal food for proper eggshell formation and skeletal growth. A large proportion of Great Tits (Pants major) in forests on nutrient-poor soils in the Netherlands produce eggs with defective shells as a result of

  1. Calcium electroporation in three cell lines; a comparison of bleomycin and calcium, calcium compounds, and pulsing conditions

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gissel, Hanne; Hojman, Pernille

    2013-01-01

    electroporation and electrochemotherapy. METHODS: The effects of calcium electroporation and bleomycin electroporation (alone or in combination) were compared in three different cell lines (DC-3F, transformed Chinese hamster lung fibroblast; K-562, human leukemia; and murine Lewis Lung Carcinoma). Furthermore...

  2. 5-HT and dopamine modulates CaV1.3 calcium channels involved in postinhibitory rebound in the spinal network for locomotion in lamprey.

    Science.gov (United States)

    Wang, Di; Grillner, Sten; Wallén, Peter

    2011-03-01

    Postinhibitory rebound (PIR) can play a significant role for producing stable rhythmic motor patterns, like locomotion, by contributing to burst initiation following the phase of inhibition, and PIR may also be a target for modulatory systems acting on the network. The current aim was to explore the PIR in one type of interneuron in the lamprey locomotor network and its dependence on low voltage-activated (LVA) calcium channels, as well as its modulation by 5-HT and dopamine. PIR responses in commissural interneurons, mediating reciprocal inhibition and left-right alternation in the network, were significantly larger than in motoneurons. The L-type calcium channel antagonist nimodipine reduced PIR amplitude by ∼ 50%, whereas the L-channel agonist BAY K 8644 enhanced PIR amplitude, suggesting that LVA calcium channels of the L-subtype (Ca(V)1.3) participate in the PIR response. The remainder of the response was blocked by nickel, indicating that T-type (Ca(V)3) LVA calcium channels also contribute. No evidence was obtained for the involvement of a hyperpolarization-activated current. Furthermore, 5-HT, acting via 5-HT(1A) receptors, reduced PIR, as did dopamine, acting via D(2) receptors. Coapplication of nimodipine caused no further PIR reduction, indicating that these modulators target Ca(V)1.3 channels specifically. These results suggest that PIR may play a prominent role in the generation of alternating network activity and that the Ca(V)1.3 and Ca(V)3 subtypes of LVA calcium channels together underlie the PIR response. 5-HT and dopamine both target PIR via Ca(V)1.3 channels, which may contribute significantly to their modulatory influence on locomotor network activity.

  3. Epigenetic Mechanisms Underlie Genome Development

    Science.gov (United States)

    Lamm, Ehud

    2013-01-01

    Technological and methodological advances, in particular next-generation sequencing and chromatin profiling, has led to a deluge of data on epigenetic mechanisms and processes. Epigenetic regulation in the brain is no exception. In this commentary, Ehud Lamm writes that extending existing frameworks for thinking about psychological development to…

  4. Calcium and Iron Levels in Some Fruits and Vegetables Commonly ...

    African Journals Online (AJOL)

    , Cabbage, Pepper, Spinach, and Tomato) in each case were analysed for their Calcium and iron levels using spectrophotometric method of analysis; From the results, it was found that the concentration of Calcium was highest in spinach ...

  5. Calcium Supplements: A Risk Factor for Heart Attack?

    Science.gov (United States)

    ... for heart attack? I've read that calcium supplements may increase the risk of heart attack. Is ... Some doctors think it's possible that taking calcium supplements may increase your risk of a heart attack. ...

  6. Calcium Supplements: Do They Interfere with Blood Pressure Drugs?

    Science.gov (United States)

    ... blood pressure drugs? Is it true that calcium supplements may interact with blood pressure medications? Answers from ... Sheps, M.D. Yes. In large amounts, calcium supplements may interact with some blood pressure medications. Interactions ...

  7. The effect of farmyard manure and calcium ammonium nitrate ...

    African Journals Online (AJOL)

    The effect of farmyard manure and calcium ammonium nitrate fertilisers on micronutrient density (iron, zinc, manganese, calcium and potassium) and seed yields of solanium villosum (black nightshade) and cleome gynandra (cat whiskers) on uetric nitisol.

  8. The role of trace metals in calcium urolithiasis.

    Science.gov (United States)

    Meyer, J L; Angino, E E

    1977-03-01

    Ten urinary stones composed of calcium oxalate or a mixture of calcium oxalate and calcium phosphate were analyzed for trace metal content by emission spectroscopy. Trace metals found in amounts of 0.001 per cent or more were iron, copper, zinic, tin, lead, and aluminum. The inhibitory effect of each of these trace metals on the crystal growth of calcium oxalate and calcium phosphate was tested. Results indicated that none of the metal affect the crystal growth of calcium oxalate at concentrations approximating those found in normal urine. The metal ions copper (II), zinc (II), tin (II), and aluminum (III) did affect the crystal growth of calcium phosphate when present at physiologic concentrations; however, their contribution to the total calcium phosphate inhibitor activity in urine was estimated to be insufficient to have a regulatory role in urinary stone growth.

  9. Similarities and differences between calcium antagonists: pharmacological aspects

    NARCIS (Netherlands)

    van Zwieten, P. A.; Pfaffendorf, M.

    1993-01-01

    Characteristics of three different calcium antagonist groups: Most important calcium antagonists used to treat cardiovascular disease belong to one of three main groups, phenylalkylamines, dihydropyridines and benzothiazepines. The best known drug in each group is verapamil, nifedipine and

  10. Protective effects of calcium antagonists in different organs and tissues

    NARCIS (Netherlands)

    van Zwieten, P. A.

    1993-01-01

    The therapeutic efficacy of calcium antagonists in ischemic disorders of various tissues is attributed to vasodilator and antivasoconstrictor activities. A direct, energy-conserving, antiischemic effect of certain calcium antagonists has been claimed repeatedly by basic scientists. The clinical

  11. Mucins and calcium phosphate precipitates additively stimulate cholesterol crystallization

    NARCIS (Netherlands)

    van den Berg, A. A.; van Buul, J. D.; Tytgat, G. N.; Groen, A. K.; Ostrow, J. D.

    1998-01-01

    Human biliary mucin and calcium binding protein (CBP) influence formation of both calcium salt precipitates and cholesterol crystals and colocalize in the center of cholesterol gallstones. We investigated how physiological concentrations of these proteins regulate cholesterol crystallization in

  12. Development of calcium phosphate based apatite from hen's eggshell

    Indian Academy of Sciences (India)

    Unknown

    Cowin et al 1987). The apatitic calcium phosphate of bone mineral consists of carbonate, small amount of sodium, magnesium and other trace ele- ments. The submicroscopic crystal of calcium phosphate in bone resembles the crystal structure ...

  13. Calcium phosphate saturation in seawater around the Andaman Island

    Digital Repository Service at National Institute of Oceanography (India)

    Naik, S.; Reddy, C.V.G.

    Ionic product (IP) of calcium phosphate is calculated at some stations around Andaman Island. The depthwise variations of the ionic product of calcium phosphate seem to follow a normal trend with maximum saturation value between 100 to 200 m. Using...

  14. Calcium absorption from corn tortilla is relatively high and is dependent upon calcium content and liming in Mexican women.

    Science.gov (United States)

    Rosado, Jorge L; Díaz, Margarita; Rosas, Angélica; Griffit, Ian; García, Olga P

    2005-11-01

    Corn tortillas are the staple food of Mexico. During their preparation, calcium is added to the tortillas; therefore, tortillas are the main source of calcium for a large proportion of the population. The bioavailability of calcium from lime-treated tortillas in humans is not known. The objectives of the present study were to determine calcium absorption from corn tortilla, to determine the effect of lime treatment on calcium absorption from corn tortilla, and to compare calcium absorption from tortilla prepared with a commercial corn flour and tortillas prepared with the traditional lime treatment at home. Nonpregnant, nonlactating women (n = 9) were administered 3 different treatments: 1) 180 g of corn tortilla prepared from corn flour with no lime treatment (CF), 2) 180 g of corn tortilla prepared from lime-treated commercial corn flour (LTCCF), or 3) 180 g of corn tortillas prepared from lime-treated home-prepared corn flour (LTHCF). Calcium absorption was measured using an established dual-tracer stable isotope technique. Calcium absorption of CF, LTCCF, and LTHCF was (mean +/- SD): 44 +/- 3.2, 32 +/- 4.4, and 30 +/- 2.4%, respectively; the fractional calcium absorption from CF differed from that of either LTCCF or LTHCF (P corn tortillas is high and dependent on calcium concentration. The addition of calcium during lime treatment increases calcium concentration and total calcium absorption.

  15. Faecal calcium excretion does not decrease during long-term feeding of a low-calcium diet in adult dogs.

    Science.gov (United States)

    Schmitt, S; Mack, J; Kienzle, E; Alexander, L G; Morris, P J; Colyer, A; Dobenecker, B

    2018-04-01

    According to a previous meta-analysis, adult dogs do not notably increase calcium absorption from the gastrointestinal tract when calcium intake is decreased. This results in a negative calcium balance even with a moderate calcium reduction. In this study we wanted to verify (i) whether a negative calcium balance occurs at a calcium intake equivalent to NRC (2006) (Nutrient requirements of dogs and cats, 2006, The National Academies Press, Washington, DC) minimal requirements, and if so (ii) whether the negative calcium balance will persist for up to 6 months on a low-calcium diet. After a pre-feeding period of at least 18 weeks with calcium intake slightly exceeding maintenance requirements (200 mg/kg body weight 0.75 ), 12 dogs (6 Beagles, 6 Foxhound crossbreds) were fed a low-calcium diet for 28 weeks. One dog was removed from the trial for reasons unrelated to the study at week 23. Calcium intake amounted to 60 mg/kg body weight 0.75 corresponding to the minimal requirement for maintenance in dogs (NRC, 2006 (Nutrient requirements of dogs and cats, 2006, The National Academies Press, Washington, DC)). Digestion trials were carried out at week 7, 14, 21 and 28 of the low calcium feeding period. At these time points, and at week 18 of the pre-trial, blood samples were taken and analysed for calcium, ionised calcium, phosphorus, parathyroid hormone, vitamin D, serum crosslaps and bone alkaline phosphatase. Apparent calcium digestibility was negative throughout the study, suggesting a negative calcium balance. There was no systematic decrease in faecal calcium excretion. Serum calcium, ionised calcium and phosphorus remained within the reference range. Serum crosslaps increased continuously from baseline to week 28 of trial, with averages increasing from 0.102 ng/ml to 0.279 ng/ml, suggesting osteoclastic activity, indicative of calcium mobilisation from the skeleton. The study supports the theory of a lack of adaptation of intestinal calcium absorption from

  16. Calcium hydroxylapatite for jawline rejuvenation: consensus recommendations.

    Science.gov (United States)

    Dallara, Jean-Marie; Baspeyras, Martine; Bui, Patrick; Cartier, Hugues; Charavel, Marie-Hélène; Dumas, Laurent

    2014-03-01

    Age-associated volume loss is now known to play an important role in the structural changes of the aging face. In the lower face, this manifests as drooping of the corners of the mouth and jowl leading to a loss of the oval jawline of youth. Jawline reshaping by replacing volume has therefore become an indispensable component of modern facial rejuvenation. Calcium hydroxylapatite (CaHA; Radiesse® , Merz Pharmaceuticals GmbH, Frankfurt, Germany) is an injectable filler with a cosmetic indication for tissue augmentation. The ability of calcium hydroxylapatite to provide immediate and long-lasting volume enhancement makes it an ideal agent for restoring an oval jawline. This consensus statement has been developed to assist clinicians who would like to gain more experience in the use of volumizing agents to achieve an optimal outcome with this procedure. Using the recently developed Merz Aesthetics Scale® for jawline, the consensus provides a treatment protocol for individuals at each stage of oval loss and presents a series of before and after images to illustrate the improvements that can be achieved. Specific recommendations for calcium hydroxylapatite including type of anesthesia, injection techniques, volume for injection, use in combination with other procedures, and expected duration of corrections are provided. Techniques for minimizing and managing expected problems and potential complications are also described. Calcium hydroxylapatite is appropriate for treating patients at any stage of oval loss. © 2014 Wiley Periodicals, Inc.

  17. CALCIUM DEFICIENCY AND CAUSATION OF RICKETS IN ...

    African Journals Online (AJOL)

    hi-tech

    2005-03-03

    Mar 3, 2005 ... Objective: To assess the role of calcium in the development of clinical rickets among. Ethiopian children coming to Jimma Specialised Hospital outpatient, department. Design: Case control study. Settings: Jimma Specialised Teaching Hospital and surrounding urban and rural community in the catchment ...

  18. Calcium chloride improve ethanol production in recombinant ...

    African Journals Online (AJOL)

    hope&shola

    2010-11-08

    Nov 8, 2010 ... significantly improve the ethanol production. This was also clearly ... parameter values over time in Z.M.F-4 under high sugar osmotic stress. Calcium chloride .... These genes were introduced into Z. mobilis ATCC 31821 by the transposition method as described in the literature (Foulongne et al., 1999). The.

  19. 21 CFR 172.410 - Calcium silicate.

    Science.gov (United States)

    2010-04-01

    ... CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Anticaking... agent in food in an amount not in excess of that reasonably required to produce its intended effect. (b... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium silicate. 172.410 Section 172.410 Food and...

  20. Isolation and characterization of biogenic calcium carbonate ...

    Indian Academy of Sciences (India)

    Bacterial adhesion result reveals that YSZ coating drastically reduce bacterial invasion than titanium substrate. Keywords. Oral bacteria; bioceramic; dental implant; YSZ .... ity of the cell [15]. Figure 3c shows the schematic view of calcium precipitation from the oral bacteria which constitutes three major metabolic activities to ...

  1. 21 CFR 582.3225 - Calcium sorbate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium sorbate. 582.3225 Section 582.3225 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Chemical Preservatives § 582...

  2. 21 CFR 582.3189 - Calcium ascorbate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium ascorbate. 582.3189 Section 582.3189 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Chemical Preservatives § 582...

  3. 21 CFR 582.3221 - Calcium propionate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium propionate. 582.3221 Section 582.3221 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Chemical Preservatives § 582...

  4. 21 CFR 182.3189 - Calcium ascorbate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium ascorbate. 182.3189 Section 182.3189 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Chemical Preservatives § 182.3189...

  5. Laterality of Symptomatic Recurrent Calcium Nephrolithiasis | Ketata ...

    African Journals Online (AJOL)

    Objective: Although it is presumed that both kidneys excrete similar urinary constituents, it is a general observation that the majority of patients present with unilateral stone disease. The aim of this work was to study the laterality of recurrence in calcium stone formers. Patients and Methods: In a retrospective study of 154 ...

  6. Calcium carbonate precipitation by different bacterial strains ...

    African Journals Online (AJOL)

    Bacteria are capable of performing metabolic activities which thereby promote precipitation of calcium carbonate in the form of calcite. In this study, it is shown that microbial mineral precipitation was a result of metabolic activities of some specific microorganisms. Concrete microorganisms were used to improve the overall ...

  7. Scattering lengths of calcium and barium isotopes

    NARCIS (Netherlands)

    Dammalapati, U.; Willmann, L.; Knoop, S.

    2011-01-01

    We have calculated the s-wave scattering length of all the even isotopes of calcium (Ca) and barium (Ba) in order to investigate the prospect of Bose-Einstein condensation (BEC). For Ca we have used an accurate molecular potential based on detailed spectroscopic data. Our calculations show that Ca

  8. Pharmacological analysis of calcium antagonist receptors

    International Nuclear Information System (INIS)

    Reynolds, I.J.

    1987-01-01

    This work focuses on two aspects of the action of calcium antagonist drugs, namely, the interaction of drugs with receptors for verapamil-like calcium antagonists, and the interactions of drugs with voltage-sensitive calcium fluxes in rat brain synaptosomes. From binding studies I have found that the ligand of choice for labeling the verapamil receptor is (-)[ 3 H]desmethoxy-verapamil. This drug labels potently, reversibly and stereoselectively two receptors in membranes prepared from rat brain and rabbit skeletal muscle tissues. In equilibrium studies dihydropyridine calcium antagonists interact in a non-competitive fashion, while many non-DHPs are apparently competitive. In-depth kinetic studies in skeletal muscle membranes indicate that the two receptors are linked in a negative heterotropic fashion, and that low-affinity binding of (-) [ 3 H]desmethoxy-verapamil may be to the diltiazem receptor. However, these studies were not able to distinguish between the hypothesis that diltiazem binds to spatially separate, allosterically coupled receptors, and the hypothesis that diltiazem binds to a subsite of the verapamil receptor

  9. Thermoluminescence dosimetry of rare earth doped calcium ...

    Indian Academy of Sciences (India)

    The thermoluminescence (TL) properties of calcium aluminate (CaAl2O4) doped with different rare earth ions have been studied and their suitability for radiation dosimetry applications is discussed. It is observed that monocalcium aluminate doped with cerium is a good dosimeter having linear response up to about 4 kGy of ...

  10. [Intra-cystic renal calcium milk].

    Science.gov (United States)

    Meunier, B; Médart, L; Massart, J P; Collignon, L

    2015-02-01

    Intra-cystic renal calcium milk is a rare entity. The authors report a clinical case, and describe the radiographic and tomodensitometric appearances. This 50 year old patient has been followed up for more than ten years for urinary lithiasis with recurrent pain.

  11. Effect of Ultrasound on Calcium Carbonate Crystallization

    NARCIS (Netherlands)

    Wagterveld, R.M.

    2013-01-01

    Scaling comprises the formation of hard mineral deposits on process or membrane equipment and calcium carbonate is the most common scaling salt. Especially in reverse osmosis (RO) membrane systems, scale formation has always been a serious limitation, causing flux decline, membrane degradation, loss

  12. Calcium, channels, intracellular signaling and autoimmunity.

    Science.gov (United States)

    Izquierdo, Jorge-Hernán; Bonilla-Abadía, Fabio; Cañas, Carlos A; Tobón, Gabriel J

    2014-01-01

    Calcium (Ca²⁺) is an important cation able to function as a second messenger in different cells of the immune system, particularly in B and T lymphocytes, macrophages and mastocytes, among others. Recent discoveries related to the entry of Ca²⁺ through the store-operated calcium entry (SOCE) has opened a new investigation area about the cell destiny regulated by Ca²⁺ especially in B and T lymphocytes. SOCE acts through calcium-release-activated calcium (CRAC) channels. The function of CRAC depends of two recently discovered regulators: the Ca²⁺ sensor in the endoplasmic reticulum or stromal interaction molecule (STIM-1) and one subunit of CRAC channels called Orai1. This review focuses on the role of Ca²⁺ signals in B and T lymphocytes functions, the signalling pathways leading to Ca²⁺ influx, and the relationship between Ca²⁺ signals and autoimmune diseases. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  13. Serum Calcium, Inorganic Phosphates and some Haematological ...

    African Journals Online (AJOL)

    Objectives: Sickle cell disease has long been associated with bone deformities and pain. Mineral salts such as calcium and inorganic phosphate are critical in bone formation and metabolism. This investigation was designed to study the serum concentration of these minerals as well as some haematological parameters in ...

  14. Calcium and M'yocardial Infarction

    African Journals Online (AJOL)

    1974-03-16

    Mar 16, 1974 ... Associated risk factors apart, attention has been directed at other possible ... later T-wave inversion, a falling R wave in the praecordial leads, complete left ... TABLE I. SERUM CALCIUM LEVELS RELATIVE TO AGE AND SEX IN 75 PATIENTS WITH MYOCARDIAL INFARCTION. 5.0. 00 •. O. 0e4i...... •. 0000.

  15. How calcium makes endocytic receptors attractive

    DEFF Research Database (Denmark)

    Andersen, Christian B F; Moestrup, Søren K

    2014-01-01

    'lynchpin' that stabilizes favorable positioning of ligand-attractive receptor residues. In addition to explaining how calcium depletion can cause ligand-receptor dissociation, the new data add further insight into how acidification contributes to dissociation through structural changes that affect...

  16. An improved calcium chloride method preparation and ...

    African Journals Online (AJOL)

    method, improved from a classical protocol, has made some modifications on the concentration of calcium chloride and competent bacteria solution, rotation speed in centrifugation and centrifugation time. It was found that the optimal transformation efficiency were obtained when the concentration of CaCl2 was 75 mmol/l, ...

  17. Calcium antagonists for aneurysmal subarachnoid haemorrhage

    NARCIS (Netherlands)

    Rinkel, G. J. E.; Feigin, V. L.; Algra, A.; van den Bergh, W. M.; Vermeulen, M.; van Gijn, J.

    2005-01-01

    BACKGROUND: Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage (SAH). Its pathogenesis has not been elucidated yet, but may be related to vasospasm. Experimental studies have indicated that calcium antagonists can prevent or reverse vasospasm and have

  18. Mechanism of unusual polymorph transformations in calcium ...

    Indian Academy of Sciences (India)

    research for many years. However, till date the ... Polymorph selection plays key role in biominerali- zation as the .... Mechanism of unusual polymorph transformations in calcium carbonate. 1401. In te n s ity. 2-Theta - Scale. 20. 30. 40. 50. 60. V. V110. V. V. V. V. V. Refluxed for 75 mins: 100% Aragonite. A221. A. A. A. A. A.

  19. Calcium model for mammalian skeletal muscle

    NARCIS (Netherlands)

    Wallinga, W.; Boom, H.B.K.; Heijink, R.J.; van der Vliet, G.H.

    1981-01-01

    A model is presented describing quantitatively the events between excitation and force development in skeletal muscle. It consists of a calcium mediated activation model (c.m.a.m.) in series with a force generator model (f.g.m.). The c.m.a.m. was based on intracellular processes such as cisternal

  20. Thermoluminescence dosimetry of rare earth doped calcium ...

    Indian Academy of Sciences (India)

    Unknown

    Calcium aluminate crystals can also exist in mono- clinic as well as orthorhombic structures (Dougill 1957). Many researchers have studied CaAl2O4 as an important constituent of cementitious compositions (Mohamed and. Sharp 1997). Of late, the thrust is on its use as lumines- cent host. Several reports dealing with the ...

  1. Modularized study of human calcium signalling pathway

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    Modularization is a process by which we can break a network into small units for better analysis of the original network. The idea is used here to break human calcium signalling pathway into simple entities known as modules. Since there is no single definition of a module, we have followed certain criteria to create them.

  2. Physicochemical characterization of zinc-substituted calcium ...

    Indian Academy of Sciences (India)

    In this paper the incorporation of the Zn ions into natural and synthetic calcium phosphates has been reported. Natural hydroxyapatites (HAs) applied in this study were derived mainly from pork bones whereas both brushite and synthetic were formed using wet chemical methods. Ambient temperature synthesis leads to the ...

  3. Calcium concentration in the CAPD dialysate

    DEFF Research Database (Denmark)

    Bro, S; Brandi, L; Daugaard, H

    1998-01-01

    for the progression of secondary hyperparathyroidism. When hypercalcemia was present in combination with suppressed PTH levels, a controlled increase of PTH could be obtained with a temporary discontinuation of vitamin D and/or a reduction of calcium carbonate treatment in combination with a dialysate Ca...

  4. CALCIUM DEFICIENCY AND CAUSATION OF RICKETS IN ...

    African Journals Online (AJOL)

    hi-tech

    2005-03-03

    Mar 3, 2005 ... In rats the rate of inactivation of 25- hydioxycholecalciferol (25-OHD) in the liver is increased by calcium deprivation (or increased phytic acid). The effect is mediated by 1,25 dihydroxy-cholecalciferol (1,25. (OH)2D) produced in response to secondary hyperparathyroidism(l3). Studies conducted in Nigeria.

  5. Biocompatibility of bio based calcium carbonate nanocrystals ...

    African Journals Online (AJOL)

    Background: Currently, there has been extensive research interest for inorganic nanocrystals such as calcium phosphate, iron oxide, silicone, carbon nanotube and layered double hydroxide as a drug delivery system especially in cancer therapy. However, toxicological screening of such particles is paramount importance ...

  6. Defluoridation of water using calcium aluminate material

    Czech Academy of Sciences Publication Activity Database

    Sakhare, N.; Lunge, S.; Rayalu, S.; Bakardjieva, Snejana; Šubrt, Jan; Devotta, S.; Labhsetwar, N.

    2012-01-01

    Roč. 203, SEPTEMBER (2012), s. 406-414 ISSN 1385-8947 R&D Projects: GA MŠk LC523 Institutional support: RVO:61388980 Keywords : Defluoridation * Fluorosis * Adsorption * Fluoride removal * Calcium aluminate Subject RIV: CA - Inorganic Chemistry Impact factor: 3.473, year: 2012

  7. Phosphorylation of erythrocyte membrane liberates calcium

    International Nuclear Information System (INIS)

    Chauhan, V.P.S.; Brockerhoff, H.

    1986-01-01

    Phosphorylation of permeabilized erythrocyte ghost membranes with ATP results in an increase free calcium level as measured with the help of Ca 2+ electrode and 45 Ca. This effect could not be observed in the presence of p - chloromercuric benzoate, an inhibitor of kinases. The rise in the free calcium due to phosphorylation of the membrane was accompanied by a decrease in the level of phosphatidylinositol (PI) and an increase in phosphatidylinositolmonophosphate (PIP) and phosphatidylinositolbisphosphate (PIP 2 ). These results support the proposal that an inositol shuttle, PI ↔ PIP ↔ PIP 2 , operates to maintain the intracellular calcium concentration. The cation is believed to be sequestered in a cage formed by the head groups of two acidic phospholipid molecules, e.g., phosphatidylserine and phosphatidylinositol, with the participation of both PO and fatty acid ester CO groups. When the inositol group of such a cage is phosphorylated, inter-headgroup hydrogen bonding between the lipids is broken. As a result the cage opens and calcium is released

  8. Urinary calcium, sodium, and bone mass of young females.

    Science.gov (United States)

    Matkovic, V; Ilich, J Z; Andon, M B; Hsieh, L C; Tzagournis, M A; Lagger, B J; Goel, P K

    1995-08-01

    Calcium is an important determinant of peak bone mass in young adults because of its influence on skeletal development during growth. Attainment of maximum peak bone mass requires optimal positive balance between calcium intake and obligatory losses of calcium, primarily in urine and feces. Urinary excretion is an important determinant of calcium retention in the body. Accordingly, the purpose of this study was to evaluate the influence of various nutrients on urinary calcium excretion, and to assess their impact on bone mass of young females, aged 8-13 y, during early puberty. The study was conducted in 381 healthy white females in pubertal stage 2. From each participant we collected basic anthropometric measurements, a 3-d food record, blood, a 24-h urine sample, and bone mass measurements of the total body and forearm by dual X-ray absorptiometry. Urinary sodium was found to be one of the most important determinants of urinary calcium excretion: [urinary calcium (mmol/d) = 0.01154 x urinary sodium (mmol/d) + 0.823], whereas calcium intake had relatively little impact: [urinary calcium (mmol/d) = 0.02252 x calcium intake (mmol/d) + 1.5261]. Urinary calcium was much higher at a calcium intake of approximately 37.5 mmol/d (1500 mg/d), supporting the notion that calcium is a threshold nutrient. Calcium intake had a significant positive influence on the bone mineral content and density of the whole body and radius shaft whereas urinary calcium had a negative influence, presumably by reducing calcium accretion into the skeleton.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Effects of calcium channel on ovarian cancer cells

    OpenAIRE

    Zhang, Chunyun; Li, Hailing

    2017-01-01

    The aim of the present study was to examine the effects of calcium channel protein on ovarian cancer cells. The expression of calcium channel protein in normal ovarian cells and ovarian cancer cells was detected by fluorescence quantitative PCR. Subsequently, the ovarian cancer cells were added to calcium channel protein activator media at various concentrations of 0, 1, 4, 8, 12, 16 and 20 mmol/l. The concentration of calcium ion in different samples was produced, and using an MTT assay, ova...

  10. NbIT--a new information theory-based analysis of allosteric mechanisms reveals residues that underlie function in the leucine transporter LeuT.

    Science.gov (United States)

    LeVine, Michael V; Weinstein, Harel

    2014-05-01

    Complex networks of interacting residues and microdomains in the structures of biomolecular systems underlie the reliable propagation of information from an input signal, such as the concentration of a ligand, to sites that generate the appropriate output signal, such as enzymatic activity. This information transduction often carries the signal across relatively large distances at the molecular scale in a form of allostery that is essential for the physiological functions performed by biomolecules. While allosteric behaviors have been documented from experiments and computation, the mechanism of this form of allostery proved difficult to identify at the molecular level. Here, we introduce a novel analysis framework, called N-body Information Theory (NbIT) analysis, which is based on information theory and uses measures of configurational entropy in a biomolecular system to identify microdomains and individual residues that act as (i)-channels for long-distance information sharing between functional sites, and (ii)-coordinators that organize dynamics within functional sites. Application of the new method to molecular dynamics (MD) trajectories of the occluded state of the bacterial leucine transporter LeuT identifies a channel of allosteric coupling between the functionally important intracellular gate and the substrate binding sites known to modulate it. NbIT analysis is shown also to differentiate residues involved primarily in stabilizing the functional sites, from those that contribute to allosteric couplings between sites. NbIT analysis of MD data thus reveals rigorous mechanistic elements of allostery underlying the dynamics of biomolecular systems.

  11. Does Growth in the Executive System of Working Memory Underlie Growth in Literacy for Bilingual Children With and Without Reading Disabilities?

    Science.gov (United States)

    Swanson, H Lee; Orosco, Michael J; Kudo, Milagros

    This cohort-sequential study explored the components of working memory (WM) that underlie second language (L2) reading growth in 450 children at risk and not at risk for reading disabilities (RD) whose first language is Spanish. English language learners designated as balanced and nonbalanced bilinguals with and without risk for RD in Grades 1, 2, and 3 at Wave 1 were administered a battery of cognitive (short-term memory, WM, naming speed, and inhibition), vocabulary, and reading measures in Spanish and English. These same measures were administered 1 and 2 years later. Two important findings occurred: First, growth in the WM executive component was significantly related to growth in English word identification and passage comprehension when competing measures (phonological processing, naming speed, inhibition, and fluid intelligence) were entered into the multilevel growth model. Second, children defined as at risk for RD in Wave 1 had lower intercepts than children not at risk at Wave 3 across several measures of cognition, language, and achievement. However, except on measures of the executive component of WM, no significant group differences in linear growth emerged. These findings suggest that growth in L2 reading was tied to growth in the executive system of WM.

  12. Neurons That Underlie Drosophila melanogaster Reproductive Behaviors: Detection of a Large Male-Bias in Gene Expression in fruitless-Expressing Neurons

    Directory of Open Access Journals (Sweden)

    Nicole R. Newell

    2016-08-01

    Full Text Available Male and female reproductive behaviors in Drosophila melanogaster are vastly different, but neurons that express sex-specifically spliced fruitless transcripts (fru P1 underlie these behaviors in both sexes. How this set of neurons can generate such different behaviors between the two sexes is an unresolved question. A particular challenge is that fru P1-expressing neurons comprise only 2–5% of the adult nervous system, and so studies of adult head tissue or whole brain may not reveal crucial differences. Translating Ribosome Affinity Purification (TRAP identifies the actively translated pool of mRNAs from fru P1-expressing neurons, allowing a sensitive, cell-type-specific assay. We find four times more male-biased than female-biased genes in TRAP mRNAs from fru P1-expressing neurons. This suggests a potential mechanism to generate dimorphism in behavior. The male-biased genes may direct male behaviors by establishing cell fate in a similar context of gene expression observed in females. These results suggest a possible global mechanism for how distinct behaviors can arise from a shared set of neurons.

  13. Bariatric Surgery in Obese Women of Reproductive Age Improves Conditions That Underlie Fertility and Pregnancy Outcomes: Retrospective Cohort Study of UK National Bariatric Surgery Registry (NBSR).

    Science.gov (United States)

    Edison, Eric; Whyte, Martin; van Vlymen, Jeremy; Jones, Simon; Gatenby, Piers; de Lusignan, Simon; Shawe, Jill

    2016-12-01

    The aims of this study are the following: to describe the female population of reproductive age having bariatric surgery in the UK, to assess the age and ethnicity of women accessing surgery, and to assess the effect of bariatric surgery on factors that underlie fertility and pregnancy outcomes. Demographic details, comorbidities, and operative type of women aged 18-45 years were extracted from the National Bariatric Surgery Registry (NBSR). A comparison was made with non-operative cases (aged 18-45 and BMI ≥40 kg/m 2 ) from the Health Survey for England (HSE, 2007-2013). Analyses were performed using "R" software. Data were extracted on 15,222 women from NBSR and 1073 from HSE. Women aged 18-45 comprised 53 % of operations. Non-Caucasians were under-represented in NBSR compared to HSE (10 vs 16 % respectively, p fertility and pregnancy outcomes. A prospective study is required to verify these effects.

  14. Conductance of single-atom platinum contacts: Voltage dependence of the conductance histogram

    DEFF Research Database (Denmark)

    Nielsen, S.K.; Noat, Y.; Brandbyge, Mads

    2003-01-01

    The conductance of a single-atom contact is sensitive to the coupling of this contact atom to the atoms in the leads. Notably for the transition metals this gives rise to a considerable spread in the observed conductance values. The mean conductance value and spread can be obtained from the first...... peak in conductance histograms recorded from a large set of contact-breaking cycles. In contrast to the monovalent metals, this mean value for Pt depends strongly on the applied voltage bias and other experimental conditions and values ranging from about 1 G(0) to 2.5 G(0) (G(0)=2e(2)/h) have been...... reported. We find that at low bias the first peak in the conductance histogram is centered around 1.5 G(0). However, as the bias increases past 300 mV the peak shifts to 1.8 G(0). Here we show that this bias dependence is due to a geometric effect where monatomic chains are replaced by single-atom contacts...

  15. Ion Concentration- and Voltage-Dependent Push and Pull Mechanisms of Potassium Channel Ion Conduction.

    Directory of Open Access Journals (Sweden)

    Kota Kasahara

    Full Text Available The mechanism of ion conduction by potassium channels is one of the central issues in physiology. In particular, it is still unclear how the ion concentration and the membrane voltage drive ion conduction. We have investigated the dynamics of the ion conduction processes in the Kv1.2 pore domain, by molecular dynamics (MD simulations with several different voltages and ion concentrations. By focusing on the detailed ion movements through the pore including selectivity filter (SF and cavity, we found two major conduction mechanisms, called the III-IV-III and III-II-III mechanisms, and the balance between the ion concentration and the voltage determines the mechanism preference. In the III-IV-III mechanism, the outermost ion in the pore is pushed out by a new ion coming from the intracellular fluid, and four-ion states were transiently observed. In the III-II-III mechanism, the outermost ion is pulled out first, without pushing by incoming ions. Increases in the ion concentration and voltage accelerated ion conductions, but their mechanisms were different. The increase in the ion concentrations facilitated the III-IV-III conductions, while the higher voltages increased the III-II-III conductions, indicating that the pore domain of potassium channels permeates ions by using two different driving forces: a push by intracellular ions and a pull by voltage.

  16. Mefloquine inhibits voltage dependent Nav1.4 channel by overlapping the local anaesthetic binding site.

    Science.gov (United States)

    Paiz-Candia, Bertin; Islas, Angel A; Sánchez-Solano, Alfredo; Mancilla-Simbro, Claudia; Scior, Thomas; Millan-PerezPeña, Lourdes; Salinas-Stefanon, Eduardo M

    2017-02-05

    Mefloquine constitutes a multitarget antimalaric that inhibits cation currents. However, the effect and the binding site of this compound on Na + channels is unknown. To address the mechanism of action of mefloquine, we employed two-electrode voltage clamp recordings on Xenopus laevis oocytes, site-directed mutagenesis of the rat Na + channel, and a combined in silico approach using Molecular Dynamics and docking protocols. We found that mefloquine: i) inhibited Na v 1.4 currents (IC 50 =60μM), ii) significantly delayed fast inactivation but did not affect recovery from inactivation, iii) markedly the shifted steady-state inactivation curve to more hyperpolarized potentials. The presence of the β1 subunit significantly reduced mefloquine potency, but the drug induced a significant frequency-independent rundown upon repetitive depolarisations. Computational and experimental results indicate that mefloquine overlaps the local anaesthetic binding site by docking at a hydrophobic cavity between domains DIII and DIV that communicates the local anaesthetic binding site with the selectivity filter. This is supported by the fact that mefloquine potency significantly decreased on mutant Na v 1.4 channel F1579A and significantly increased on K1237S channels. In silico this compound docked above F1579 forming stable π-π interactions with this residue. We provide structure-activity insights into how cationic amphiphilic compounds may exert inhibitory effects by docking between the local anaesthetic binding site and the selectivity filter of a mammalian Na + channel. Our proposed synergistic cycle of experimental and computational studies may be useful for elucidating binding sites of other drugs, thereby saving in vitro and in silico resources. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Reserpine: interactions with batrachotoxin and brevetoxin sites on voltage-dependent sodium channels.

    Science.gov (United States)

    Flowers, Andrew; Onwueme, Kenolisa; Creveling, Cyrus R; Daly, John W

    2002-02-01

    Reserpine inhibited batrachotoxin-elicited sodium influx in guinea pig brain synaptoneurosomes with an IC50 of about 1 microM. In the presence of brevetoxin the IC50 increased to about 80 microM. Reserpine inhibited binding of batrachotoxinin-A [3H]benzoate ([3H]BTX-B) binding in a complex manner causing a partial inhibition from 0.001 to 0.08 microM, then a rebound stimulation from 0.1 to 0.8 microM, followed by complete inhibition by 80 microM. The stimulation was prevented by the presence of brevetoxin; reserpine then smoothly inhibited binding with an IC50 of about 1 microM. Reserpine at 1 microM slightly reduced the off-rate of [3H]BTX-B binding measured in the presence of veratridine, while at a concentration of 50 microM it enhanced the off-rate, presumably by an allosteric mechanism. Reserpine at 0.3-10 microM elicited a partial inhibition of the binding of [3H]brevetoxin-3. The local anesthetic dibucaine had effects similar to reserpine: It partially inhibited binding of [3H]brevetoxin. The presence of brevetoxin reduced the potency of dibucaine as an inhibitor of batrachotoxin-elicited sodium influx from an IC50 of about 2 microM to an IC50 of about 50 microM. The results suggest that reserpine binds at both a local anesthetic site to cause allosteric inhibition of batrachotoxin-binding and action, but that it also binds to another site causing, like brevetoxin, an enhancement of batrachotoxin-binding and action. Local anesthetics also may bind to the brevetoxin site.

  18. Down-regulation of voltage-dependent sodium channels initiated by sodium influx in developing neurons

    Energy Technology Data Exchange (ETDEWEB)

    Dargent, B.; Couraud, F. (Centre National de la Recherche Scientifique, Marseille (France))

    1990-08-01

    To address the issue of whether regulatory feedback exists between the electrical activity of a neuron and ion-channel density, the authors investigated the effect of Na{sup +}-channel activators (scorpion {alpha} toxin, batrachotoxin, and veratridine) on the density of Na{sup +} channels in fetal rat brain neurons in vitro. A partial but rapid (t{sub 1/2}, 15 min) disappearance of surface Na{sup +} channels was observed as measured by a decrease in the specific binding of ({sup 3}H)saxitoxin and {sup 125}I-labeled scorpion {beta} toxin and a decrease in specific {sup 22}Na{sup +} uptake. Moreover, the increase in the number of Na{sup +} channels that normally occurs during neuronal maturation in vitro was inhibited by chronic channel activator treatment. The induced disappearance of Na{sup +} channels was abolished by tetrodotoxin, was found to be dependent on the external Na{sup +} concentration, and was prevented when either choline (a nonpermeant ion) or Li{sup +} (a permeant ion) was substituted for Na{sup +}. Amphotericin B, a Na{sup +} ionophore, and monensin were able to mimick the effect of Na{sup +}-channel activators, while a KCl depolarization failed to do this. This feedback regulation seems to be a neuronal property since Na{sup +}-channel density in cultured astrocytes was not affected by channel activator treatment or by amphotericin B. The present evidence suggests that an increase in intracellular Na{sup +} concentration, whether elicited by Na{sup +}-channel activators or mediated by a Na{sup +} ionophore, can induce a decrease in surface Na{sup +} channels and therefore is involved in down-regulation of Na{sup +}-channel density in fetal rat brain neurons in vitro.

  19. Down-regulation of voltage-dependent sodium channels initiated by sodium influx in developing neurons

    International Nuclear Information System (INIS)

    Dargent, B.; Couraud, F.

    1990-01-01

    To address the issue of whether regulatory feedback exists between the electrical activity of a neuron and ion-channel density, the authors investigated the effect of Na + -channel activators (scorpion α toxin, batrachotoxin, and veratridine) on the density of Na + channels in fetal rat brain neurons in vitro. A partial but rapid (t 1/2 , 15 min) disappearance of surface Na + channels was observed as measured by a decrease in the specific binding of [ 3 H]saxitoxin and 125 I-labeled scorpion β toxin and a decrease in specific 22 Na + uptake. Moreover, the increase in the number of Na + channels that normally occurs during neuronal maturation in vitro was inhibited by chronic channel activator treatment. The induced disappearance of Na + channels was abolished by tetrodotoxin, was found to be dependent on the external Na + concentration, and was prevented when either choline (a nonpermeant ion) or Li + (a permeant ion) was substituted for Na + . Amphotericin B, a Na + ionophore, and monensin were able to mimick the effect of Na + -channel activators, while a KCl depolarization failed to do this. This feedback regulation seems to be a neuronal property since Na + -channel density in cultured astrocytes was not affected by channel activator treatment or by amphotericin B. The present evidence suggests that an increase in intracellular Na + concentration, whether elicited by Na + -channel activators or mediated by a Na + ionophore, can induce a decrease in surface Na + channels and therefore is involved in down-regulation of Na + -channel density in fetal rat brain neurons in vitro

  20. Voltage-dependent conductance states of a single-molecule junction

    DEFF Research Database (Denmark)

    Wang, Y F; Néel, N; Kröger, J

    2012-01-01

    Ag–Sn-phthalocyanine–Ag junctions are shown to exhibit three conductance states. While the junctions are conductive at low bias, their impedance drastically increases above a critical bias. Two-level fluctuations occur at intermediate bias. These characteristics may be used to protect a nanoscale...

  1. Bias voltage dependence of a flux-sensitive Al/GaAs/Al (SNS) interferometer

    DEFF Research Database (Denmark)

    Kutchinsky, Jonatan; Taboryski, Rafael Jozef; Hansen, Jørn Bindslev

    1999-01-01

    We report new results on interferometers based on high transparency superconductor-semiconductor-superconductor junctions composed of Al and highly doped GaAs. The fabricated devices consist of planar de-SQUID like geometries with an effective flux-sensitive area of about 100-150 mu m(2). At zero...... bias voltage the fabricated interferometers typically exhibit 3% sinusoidal modulation of the conductance as a function of a magnetic field applied perpendicular to the loop. The conductance modulation is caused by resonant Andreev states in the normal GaAs region of the device. With increasing bias...

  2. Effects of Calcium Ion, Calpains, and Calcium Channel Blockers on Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Mitsuru Nakazawa

    2011-01-01

    Full Text Available Recent advances in molecular genetic studies have revealed many of the causative genes of retinitis pigmentosa (RP. These achievements have provided clues to the mechanisms of photoreceptor degeneration in RP. Apoptosis is known to be a final common pathway in RP and, therefore, a possible therapeutic target for photoreceptor rescue. However, apoptosis is not a single molecular cascade, but consists of many different reactions such as caspase-dependent and caspase-independent pathways commonly leading to DNA fractionation and cell death. The intracellular concentration of calcium ions is also known to increase in apoptosis. These findings suggest that calpains, one of the calcium-dependent proteinases, play some roles in the process of photoreceptor apoptosis and that calcium channel antagonists may potentially inhibit photoreceptor apoptosis. Herein, the effects of calpains and calcium channel antagonists on photoreceptor degeneration are reviewed.

  3. Transfected parvalbumin alters calcium homeostasis in teratocarcinoma PCC7 cells

    DEFF Research Database (Denmark)

    Müller, B K; Kabos, P; Belhage, B

    1996-01-01

    transfected. Parvalbumin-transfected and mock-transfected cells were loaded with the calcium indicator fura-2 and were exposed, in the same dish, to different concentrations of the calcium ionophore A23187 or to KCI. The results show that parvalbumin-transfected PCC7 cells had much better calcium buffering...

  4. Calcium soil amendment increases resistance of potato to blackleg ...

    African Journals Online (AJOL)

    Soft rot incidence in the progeny tubers was also significantly reduced by the calcium treatment. In addition, calcium amendment significantly reduced (P < 0.05) soft rot losses of tubers in storage. Calcium nitrate was effective in reducing blackleg and soft rot diseases in combination with either compound D or compound S.

  5. Dietary calcium intake and sunlight exposure among children aged ...

    African Journals Online (AJOL)

    Nutritional rickets can be caused by either or both calcium and vitamin D deficiencies, and can frequently occur in Africa. In Ethiopia, limited evidence exists regarding the calcium intake of children and their sunlight exposure practices. The purpose of this study was to assess information regarding dietary calcium intake and ...

  6. Effect of nutrient calcium on the cell wall composition and ...

    African Journals Online (AJOL)

    The effect of calcium in the nutrient medium on kikuyu grass (Pennisetum clandestinum Hochst), grown in a solution culture, was investigated. Calcium had no effect on the lignin content of leaf material, but decreased the lignin content per unit stem cell wall. Calcium appeared to have no significant effect on either the ...

  7. Effect of zinc supplements on the intestinal absorption of calcium

    International Nuclear Information System (INIS)

    Spencer, H.; Rubio, N.; Kramer, L.; Norris, C.; Osis, D.

    1987-01-01

    Pharmacologic doses of zinc are widely used as zinc supplements. As calcium and zinc may compete for common absorption sites, a study was carried out on the effect of a pharmacologic dose of zinc on the intestinal absorption of calcium in adult males. The analyzed dietary zinc intake in the control studies was normal, averaging 14.6 mg/day. During the high zinc study, 140 mg zinc as the sulfate was added daily for time periods ranging from 17 to 71 days. The studies were carried out during both a low calcium intake averaging 230 mg/day and during a normal calcium intake of 800 mg/day. Calcium absorption studies were carried out during the normal and high zinc intake by using an oral tracer dose of Ca-47 and determining plasma levels and urinary and fecal excretions of Ca-47. The study has shown that, during zinc supplementation, the intestinal absorption of calcium was significantly lower during a low calcium intake than in the control study, 39.3% vs 61% respectively, p less than 0.001. However, during a normal calcium intake of 800 mg/day, the high zinc intake had no significant effect on the intestinal absorption of calcium. These studies have shown that the high zinc intake decreased the intestinal absorption of calcium during a low calcium intake but not during a normal calcium intake

  8. Global dietary calcium intake among adults: a systematic review

    Science.gov (United States)

    Purpose: Low calcium intake may adversely affect bone health in adults. Recognizing the presence of low calcium intake is necessary to develop national strategies to optimize intake. To highlight regions where calcium intake should be improved, we systematically searched for the most representative ...

  9. Does calcium constrain reproductive activity in insectivorous bats ...

    African Journals Online (AJOL)

    1996-09-13

    Sep 13, 1996 ... of reproduction in insectivorous bats. To assess the possible role of dietary calcium, we have measured bone calcium concentrations in female and male long-fingered bats. (Miniopterus schreibersil) through a full reproductive cycle. The results indicate that winter was not a period of calcium stress and ...

  10. 40 CFR 721.10011 - Barium calcium manganese strontium oxide.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Barium calcium manganese strontium... Specific Chemical Substances § 721.10011 Barium calcium manganese strontium oxide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as barium calcium...

  11. Transfected parvalbumin alters calcium homeostasis in teratocarcinoma PCC7 cells

    DEFF Research Database (Denmark)

    Müller, B K; Kabos, P; Belhage, B

    1996-01-01

    Indirect evidence supports a protective role of some EF-hand calcium-binding proteins against calcium-induced neurotoxicity. Little is known about how these proteins influence cytosolic calcium levels. After cloning the parvalbumin cDNA into an expression vector, teratocarcinoma cells (PCC7) were...

  12. Enhanced expression of a calcium-dependent protein kinase from ...

    Indian Academy of Sciences (India)

    Among the downstream targets of calcium in plants, calcium-dependent protein kinases (CDPKs) form an interesting class of kinases which are activated by calcium binding. They have been implicated in a diverse array of responses to hormonal and environmental stimuli. In order to dissect the role of CDPKs in the moss ...

  13. Altered calcium metabolism: the probable major biochemical lesion ...

    African Journals Online (AJOL)

    These data are suggestive of altered calcium metabolism impairing cell membrane stabilization, the vasorelaxing effect of calcium and cell signaling. Altered calcium metabolism may be the major biochemical lesion underlying many pathological and clinical states of lead toxicity. Journal of Biomedical Investigation Vol.

  14. Evaluation of Serum Calcium and Inorganic Phosphate Levels in ...

    African Journals Online (AJOL)

    The significantly reduced level of calcium and inorganic phosphate during pregnancy and lactation (for calcium) observed in this study is indicative of inadequate calcium intake (dietary) during pregnancy or poor adherence to antenatal prescriptions. Higher provision of these elements and enlightenment on the need for ...

  15. 21 CFR 582.6215 - Monobasic calcium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Monobasic calcium phosphate. 582.6215 Section 582.6215 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....6215 Monobasic calcium phosphate. (a) Product. Monobasic calcium phosphate. (b) Conditions of use. This...

  16. 21 CFR 182.6215 - Monobasic calcium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Monobasic calcium phosphate. 182.6215 Section 182.6215 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....6215 Monobasic calcium phosphate. (a) Product. Monobasic calcium phosphate. (b) Conditions of use. This...

  17. DMPD: Calcium signaling in lymphocytes. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18515054 Calcium signaling in lymphocytes. Oh-hora M, Rao A. Curr Opin Immunol. 200...8 Jun;20(3):250-8. (.png) (.svg) (.html) (.csml) Show Calcium signaling in lymphocytes. PubmedID 18515054 Title Calcium sign

  18. Enhanced expression of a calcium-dependent protein kinase

    Indian Academy of Sciences (India)

    Among the downstream targets of calcium in plants, calcium-dependent protein kinases (CDPKs) form an interesting class of kinases which are activated by calcium binding. They have been implicated in a diverse array of responses to hormonal and environmental stimuli. In order to dissect the role of CDPKs in the moss ...

  19. 21 CFR 182.2122 - Aluminum calcium silicate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Aluminum calcium silicate. 182.2122 Section 182.2122 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....2122 Aluminum calcium silicate. (a) Product. Aluminum calcium silicate. (b) Tolerance. 2 percent. (c...

  20. 21 CFR 582.2122 - Aluminum calcium silicate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Aluminum calcium silicate. 582.2122 Section 582.2122 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....2122 Aluminum calcium silicate. (a) Product. Aluminum calcium silicate. (b) Tolerance. 2 percent. (c...

  1. Increased serum serotonin improves parturient calcium homeostasis in dairy cows

    DEFF Research Database (Denmark)

    Hernandez Castellano, Lorenzo E; Hernandez, Laura L. Hernandez; Weaver, Samantha

    2017-01-01

    Hypocalcemia in dairy cows is caused by the sudden increase in calcium demand by the mammary gland for milk production at the onset of lactation. Serotonin (5-HT) is a key factor for calcium homeostasis, modulating calcium concentration in blood. Therefore, it is hypothesized that administration...

  2. 21 CFR 872.3250 - Calcium hydroxide cavity liner.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Calcium hydroxide cavity liner. 872.3250 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3250 Calcium hydroxide cavity liner. (a) Identification. A calcium hydroxide cavity liner is a device material intended to be applied to the interior of a...

  3. Effect of Increased Dietary Calcium on Body Weight, Food and ...

    African Journals Online (AJOL)

    Food and water intake, body weight, cardiac weight index, left ventricular weight index, renal weight index and serum calcium level were determined. The result shows that OC treated rats had significantly lower serum calcium concentration, body weight gain, food, water and calcium intake than those of the control rats.

  4. Calcium content of different compositions of gallstones and pathogenesis of calcium carbonate gallstones

    Directory of Open Access Journals (Sweden)

    Ji-Kuen Yu

    2013-01-01

    Conclusion: From our study, we found chronic and/or intermittent cystic duct obstructions and low-grade GB wall inflammation lead to GB epithelium hydrogen secretion dysfunction. Increased calcium ion efflux into the GB lumen combined with increased carbonate anion presence increases SI_CaCO3 from 1 to 22.4. Thus, in an alkaline milieu with pH 7.8, calcium carbonate begins to aggregate and precipitate.

  5. A comparative study of calcium absorption following a single serving administration of calcium carbonate powder versus calcium citrate tablets in healthy premenopausal women

    Directory of Open Access Journals (Sweden)

    Haiyuan Wang

    2014-04-01

    Full Text Available Background: Calcium is an essential mineral often taken as a daily, long-term nutritional supplement. Data suggests that once-daily dosing is important with regard to long-term compliance of both drugs and nutritional supplements. Objective: This study was undertaken to compare the bioavailability of a single serving of two calcium supplements in healthy, premenopausal women. Design: A two-period, crossover bioavailability study of a single serving of calcium citrate tablets (two tablets=500 mg calcium versus a single serving of calcium carbonate powder (one packet of powder=1,000 mg calcium was performed in healthy women aged between 25 and 45. All subjects were on a calcium-restricted diet 7 days prior to testing and fasted for 12 h before being evaluated at 0, 1, 2, and 4 h after oral administration of the test agents. Blood measurements for total and ionized calcium and parathyroid hormone were performed and adverse events were monitored. Results: Twenty-three women were evaluable with a mean age of 33.2±8.71. Results showed that administration of a single serving of a calcium carbonate powder resulted in greater absorption in total and ionized calcium versus a single serving of calcium citrate tablets at 4 h (4.25±0.21 vs. 4.16±0.16, p=0.001. There were minimal side effects and no reported serious adverse events. Conclusions: This study shows that a single serving of a calcium carbonate powder is more bioavailable than a single serving of calcium citrate tablets. This may be beneficial for long-term compliance.

  6. In vivo calcium imaging of evoked calcium waves in the embryonic cortex

    Directory of Open Access Journals (Sweden)

    Mikhail eYuryev

    2016-01-01

    Full Text Available The dynamics of intracellular calcium fluxes are instrumental in the proliferation, differentiation and migration of neuronal cells. Knowledge thus far of the relationship between these calcium changes and physiological processes in the developing brain has derived principally from ex vivo and in vitro experiments. Here, we present a new method to image intracellular calcium flux in the cerebral cortex of live rodent embryos, whilst attached to the dam through the umbilical cord. Using this approach we demonstrate induction of calcium waves by laser stimulation. These waves are sensitive to ATP-receptor blockade and are significantly increased by pharmacological facilitation of intracellular-calcium release. This approach is the closest to physiological conditions yet achieved for imaging of calcium in the embryonic brain and as such opens new avenues for the study of prenatal brain development. Furthermore, the developed method could open the possibilities of preclinical translational studies in embryos particularly important for developmentally related diseases such as schizophrenia and autism.

  7. Evaluation of pH and calcium ion release of calcium hydroxide pastes containing different substances.

    Science.gov (United States)

    Duarte, Marco Antônio Húngaro; Midena, Raquel Zanin; Zeferino, Márcia A; Vivan, Rodrigo Ricci; Weckwerth, Paulo Henrique; Dos Santos, Fernando; Guerreiro-Tanomaru, Juliane Maria; Tanomaru-Filho, Mário

    2009-09-01

    The objective of this study was to evaluate the pH and calcium ion release of calcium hydroxide pastes associated with different substances. Forty acrylic teeth with simulated root canals were divided into 4 groups according to the substance associated to the calcium hydroxide paste: chlorhexidine (CHX) in 2 formulations (1% solution and 2% gel), Casearia sylvestris Sw extract, and propylene glycol (control). The teeth with pastes and sealed coronal accesses were immersed in 10 mL deionized water. After 10 minutes, 24 hours, 48 hours, and 7, 15, and 30 days, the teeth were removed to another container, and the liquid was analyzed. Calcium ion release was measured by atomic absorption spectrophotometry, and pH readings were made with a pH meter. Data were analyzed statistically by analysis of variance and Tukey test (alpha = 0.05). Calcium analysis revealed significant differences (P .05) were observed among groups in the other periods. Regarding the pH, there were significant differences (P .05) were observed among groups. All pastes behaved similarly in terms of pH and calcium ion release in the studied periods.

  8. Ion release and mechanical properties of calcium silicate and calcium hydroxide materials used for pulp capping.

    Science.gov (United States)

    Natale, L C; Rodrigues, M C; Xavier, T A; Simões, A; de Souza, D N; Braga, R R

    2015-01-01

    To compare the ion release and mechanical properties of a calcium hydroxide (Dycal) and two calcium silicate (MTA Angelus and Biodentine) cements. Calcium and hydroxyl ion release in water from 24-h set cements were calculated from titration with HCl (n = 3). Calcium release after 7, 14, 21 and 28 days at pH 5.5 and 7.0 was measured using ICP-OES (n = 6). Flexural strength (FS) and modulus (E) were tested after 48-h storage, and compressive strength (CS) was tested after 48 h and 7 days (n = 10). Ion release and mechanical data were subjected to anova/Tukey and Kruskal-Wallis/Mann-Whitney tests, respectively (α = 0.05). Titration curves revealed that Dycal released significantly fewer ions in solution than calcium silicates (P pH 7.0, whilst at pH 5.5, it dropped significantly by 24% after 21 days (P pH 5.5, MTA Angelus released significantly more calcium than Dycal (P pH 7.0 (P pH conditions. Biodentine had substantially higher strength and modulus than MTA Angelus and Dycal, both of which demonstrated low stress-bearing capabilities. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  9. Effects of calcium hydroxide and calcium chloride addition to bentonite in iron ore pelletization.

    Science.gov (United States)

    Tugrul, Nurcan; Derun, Emek Moroydor; Pişkin, Mehmet

    2006-10-01

    Pyrite ash is created as waste from the roasting of pyrite ores during the production of sulphuric acid. These processes generate great amounts of pyrite ash waste that is generally land filled. This creates serious environmental pollution due to the release of acids and toxic substances. Pyrite ash waste can be utilized in the iron production industry as a blast furnace feed to process this waste and prevent environmental pollution. The essential parameters affecting the pelletization process of pyrite ash were studied using bentonite as a binder. Experiments were then carried out using bentonite and a mixture of bentonite with calcium hydroxide and calcium chloride in order to make the bentonite more effective. The metallurgical properties of pyrite ash, bentonite, calcium hydroxide, calcium chloride, a mixture of these and sintered pellets were studied using X-ray analysis. The crushing strength tests were carried out to investigate the strength of pyrite ash waste pellets. The results of these analyses showed that pyrite ash can be agglomerated to pellets and used in the iron production industry as a blast furnace feed. The crushing strength of the pellets containing calcium hydroxide and calcium chloride in addition to bentonite was better than the strength of pellets prepared using only bentonite binder.

  10. Embryonic mobilization of calcium in a viviparous reptile: evidence for a novel pattern of placental calcium secretion.

    Science.gov (United States)

    Fregoso, Santiago P; Stewart, James R; Ecay, Tom W

    2010-05-01

    Yolk reserves supply the majority of embryonic nutrition in squamate reptiles, including calcium. Embryos of oviparous squamates exploit the eggshell for supplemental calcium, while embryos of viviparous species may receive additional calcium via the placenta. Developmental uptake of calcium in oviparous snakes increases during the interval of greatest embryonic growth (stage 35 to parturition). However, the pattern of embryonic calcium acquisition is unknown for viviparous snakes. Furthermore, while the uterus of oviparous species transports calcium early in embryonic development during mineralization of the eggshell, the timing of uterine calcium secretion in viviparous snakes is unknown. We studied a viviparous snake, Virginia striatula, to determine the ontogenetic pattern of yolk and embryonic calcium content. The pattern of embryonic calcium uptake of V. striatula is similar to that of oviparous snakes but the sources of calcium differ. In contrast to oviparous species, embryos of V. striatula acquire half of total neonatal calcium via placental provision, of which 71% is mobilized between stage 35 and parturition. Furthermore, we report for the first time in a viviparous squamate an increase in yolk calcium content during early stages of embryonic development, indicating that uterine secretion of calcium occurs in V. striatula coincident with shelling in oviparous squamates. Thus, uterine calcium secretion in this viviparous species may either occur continuously or in two phases, coincident with the timing of shelling in oviparous species and again during the last stages of development. Whereas, the pattern of embryonic calcium acquisition in V. striatula is plesiomorphic for squamates, the pattern of uterine calcium secretion includes both retention of a plesiomorphic trait and the evolution of a novel trait. Copyright 2010 Elsevier Inc. All rights reserved.

  11. Subcellular distribution of calcium during spermatogenesis of zebrafish, Danio rerio.

    Science.gov (United States)

    Golpour, Amin; Pšenička, Martin; Niksirat, Hamid

    2017-08-01

    Calcium plays a variety of vital regulatory functions in many physiological and biochemical events in the cell. The aim of this study was to describe the ultrastructural distribution of calcium during different developmental stages of spermatogenesis in a model organism, the zebrafish (Danio rerio), using a combined oxalate-pyroantimonate technique. Samples were treated by potassium oxalate and potassium pyroantimonate during two fixation stages and examined using transmission electron microscopy to detect electron dense intracellular calcium. The subcellular distribution of intracellular calcium was characterized in spermatogonium, spermatocyte, spermatid, and spermatozoon stages. The area which is covered by intracellular calcium in different stages was quantified and compared using software. Isolated calcium deposits were mainly detectable in the cytoplasm and the nucleus of the spermatogonium and spermatocyte. In the spermatid, calcium was partially localized in the cytoplasm as isolated deposits. However, most calcium was transformed from isolated deposits into an unbound pool (free calcium) within the nucleus of the spermatid and the spermatozoon. Interestingly, in the spermatozoon, calcium was mainly localized in a form of an unbound pool which was detectable as an electron-dense mass within the nucleus. Also, sporadic calcium deposits were scattered in the midpiece and flagellum. The proportional area which was covered by intracellular calcium increased significantly from early to late stages of spermatogenesis. The extent of the area which was covered by intracellular calcium in the spermatozoon was the highest compared to earlier stages. Calcium deposits were also observed in the somatic cells (Sertoli, myoid, Leydig) of zebrafish testis. The notable changes in the distribution of intracellular calcium of germ cells during different developmental stages of zebrafish spermatogenesis suggest its different homeostasis and physiological functions during the

  12. Parents' Calcium Knowledge Is Associated with Parental Practices to Promote Calcium Intake among Parents of Early Adolescent Children

    Science.gov (United States)

    Gunther, Carolyn W.; Rose, Angela M.; Bruhn, Christine; Cluskey, Mary; Reicks, Marla; Richards, Rickelle; Wong, Siew Sun; Boushey, Carol J.; Misner, Scottie; Olson, Beth

    2015-01-01

    The study reported here aimed to identify the relationship of parents' calcium knowledge with diet-related parental practices and determinants of calcium knowledge. A cross-sectional survey was conducted measuring parental practices, calcium knowledge, and demographics. A convenience sample of 599 racially/ethnically diverse parents of children…

  13. Dietary calcium but not elemental calcium from supplements is associated with body composition and obesity in Chinese women.

    Science.gov (United States)

    Huang, Lina; Xue, Jingyi; He, Ying; Wang, Jian; Sun, Changhao; Feng, Rennan; Teng, Jianhua; He, Yonghan; Li, Ying

    2011-01-01

    We assessed whether dietary calcium intake or calcium supplements associated with body composition and obesity in a Chinese population. A cross-sectional survey was performed in a population of 8940, aged 20 to 74 y. 8127 participants responded (90.9%). Height, weight, fat mass (FM), waist circumference (WC) and hip circumference were measured. Obesity definition: body mass index (BMI) ≥28 kg/m(2) (overall obesity); WC ≥85 cm for men or ≥80 cm for women (abdominal obesity І) and waist hip ratio (WHR) ≥0.90 for men or ≥0.85 for women (abdominal obesity П). The data on dietary calcium and calcium supplements were collected using food-frequency questionnaire and self-report questionnaire. Multivariate linear and multivariable logistic regressions were used to examine the associations between dietary calcium intake or calcium supplements and body composition and obesity. The average dietary calcium intake of all subjects was 430 mg/d. After adjusting for potential confounding factors, among women only, negative associations were observed between habitual dietary calcium intake and four measures of body composition (β, -0.086, P0.05). Similarly, among both men and women, we did not observe significant associations between calcium supplements and any measures of body composition or abdominal obesity (P>0.05). Dietary calcium from food rather than elemental calcium from calcium supplements has beneficial effects on the maintenance of body composition and preventing abdominal obesity in Chinese women.

  14. Dietary calcium but not elemental calcium from supplements is associated with body composition and obesity in Chinese women.

    Directory of Open Access Journals (Sweden)

    Lina Huang

    Full Text Available We assessed whether dietary calcium intake or calcium supplements associated with body composition and obesity in a Chinese population.A cross-sectional survey was performed in a population of 8940, aged 20 to 74 y. 8127 participants responded (90.9%. Height, weight, fat mass (FM, waist circumference (WC and hip circumference were measured. Obesity definition: body mass index (BMI ≥28 kg/m(2 (overall obesity; WC ≥85 cm for men or ≥80 cm for women (abdominal obesity І and waist hip ratio (WHR ≥0.90 for men or ≥0.85 for women (abdominal obesity П. The data on dietary calcium and calcium supplements were collected using food-frequency questionnaire and self-report questionnaire. Multivariate linear and multivariable logistic regressions were used to examine the associations between dietary calcium intake or calcium supplements and body composition and obesity.The average dietary calcium intake of all subjects was 430 mg/d. After adjusting for potential confounding factors, among women only, negative associations were observed between habitual dietary calcium intake and four measures of body composition (β, -0.086, P0.05. Similarly, among both men and women, we did not observe significant associations between calcium supplements and any measures of body composition or abdominal obesity (P>0.05.Dietary calcium from food rather than elemental calcium from calcium supplements has beneficial effects on the maintenance of body composition and preventing abdominal obesity in Chinese women.

  15. Continuous Modeling of Calcium Transport Through Biological Membranes

    Science.gov (United States)

    Jasielec, J. J.; Filipek, R.; Szyszkiewicz, K.; Sokalski, T.; Lewenstam, A.

    2016-08-01

    In this work an approach to the modeling of the biological membranes where a membrane is treated as a continuous medium is presented. The Nernst-Planck-Poisson model including Poisson equation for electric potential is used to describe transport of ions in the mitochondrial membrane—the interface which joins mitochondrial matrix with cellular cytosis. The transport of calcium ions is considered. Concentration of calcium inside the mitochondrion is not known accurately because different analytical methods give dramatically different results. We explain mathematically these differences assuming the complexing reaction inside mitochondrion and the existence of the calcium set-point (concentration of calcium in cytosis below which calcium stops entering the mitochondrion).

  16. Calcium Modulation of Plant Plasma Membrane-Bound Atpase Activities

    Science.gov (United States)

    Caldwell, C.

    1983-01-01

    The kinetic properties of barley enzyme are discussed and compared with those of other plants. Possibilities for calcium transport in the plasma membrane by proton pump and ATPase-dependent calcium pumps are explored. Topics covered include the ph phase of the enzyme; high affinity of barley for calcium; temperature dependence, activation enthalpy, and the types of ATPase catalytic sites. Attention is given to lipids which are both screened and bound by calcium. Studies show that barley has a calmodulin activated ATPase that is found in the presence of magnesium and calcium.

  17. [Milk and milk products: food sources of calcium].

    Science.gov (United States)

    Farré Rovira, Rosaura

    2015-04-07

    The importance of calcium in human nutrition, the mechanisms of absorption and excretion of the element, and the factors affecting them with special reference to dietary factors are described. After reviewing daily dietary intakes of calcium and the main contributors in European and Spanish population, recommended intakes in Spain, the Nordic countries and the United States are mentioned. In relation to the dietary sources of calcium it has to be noted that the value of a given food as a source of a nutrient depends on its content in the food, the bioavailability of the nutrient and the usual food consumption. The calcium contents of potential food sources of the element are reported and its value is estimated according to the potential absorbability of the calcium they contain. The benefits of milk and dairy products as sources of calcium are also highlighted. Populations such as children or elderly may require fortified foods or supplements to satisfy their high calcium needs, so some examples of the efficacy of this supplementation are discussed. It is concluded that food and drinks are the best choice to obtain calcium. Taking into account the calcium content, the usual portion size and the consumption habits milk and dairy products, nuts, green leafy vegetables and legumes can provide adequate amounts of calcium. However, milk and dairy products constitute the best dietary source thanks to the bioavailability of the calcium they contain. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  18. Consumption of calcium-fortified cereal bars to improve dietary calcium intake of healthy women: randomized controlled feasibility study.

    Directory of Open Access Journals (Sweden)

    Jennifer T Lee

    Full Text Available Calcium is an important structural component of the skeletal system. Although an adequate intake of calcium helps to maintain bone health and reduce the risk of osteoporosis, many women do not meet recommended daily intakes of calcium. Previous interventions studies designed to increase dietary intake of women have utilized primarily dairy sources of calcium or supplements. However, lactose intolerance, milk protein allergies, or food preferences may lead many women to exclude important dairy sources of dietary calcium. Therefore, we undertook a 9 week randomized crossover design trial to examine the potential benefit of including a non-dairy source of calcium in the diet of women. Following a 3 week run-in baseline period, 35 healthy women > 18 years were randomized by crossover design into either Group I or Group II. Group I added 2 calcium-fortified cereal bars daily (total of 400 mg calcium/day (intervention to their usual diet and Group II continued their usual diet (control. At the end of 3 weeks, diets were switched for another 3 weeks. Intakes of calcium and energy were estimated from 3-day diet and supplemental diaries. Wilcoxon signed-rank tests were used for within group comparisons and Mann Whitney U tests were used for between group comparisons of calcium and energy intake. Dietary calcium was significantly higher during intervention (1071 mg/d when participants consumed 2 calcium-fortified cereal bars daily than during the baseline (720 mg/d, P <0.0001 or control diets (775 mg/d, P = 0.0001 periods. Furthermore, the addition of 2 calcium-fortified cereal bars daily for the 3 week intervention did not significantly increase total energy intake or result in weight gain. In conclusion, consumption of calcium-fortified cereal bars significantly increased calcium intake of women. Further research examining the potential ability of fortified cereal bars to help maintain and improve bone health of women is warranted.ClinicalTrials.gov NCT

  19. Excitability in a stochastic differential equation model for calcium puffs.

    Science.gov (United States)

    Rüdiger, S

    2014-06-01

    Calcium dynamics are essential to a multitude of cellular processes. For many cell types, localized discharges of calcium through small clusters of intracellular channels are building blocks for all spatially extended calcium signals. Because of the large noise amplitude, the validity of noise-approximating model equations for this system has been questioned. Here we revisit the master equations for local calcium release, examine the multiple scales of calcium concentrations in the cluster domain, and derive adapted stochastic differential equations. We show by comparison of discrete and continuous trajectories that the Langevin equations can be made consistent with the master equations even for very small channel numbers. In its deterministic limit, the model reveals that excitability, a dynamical phenomenon observed in many natural systems, is at the core of calcium puffs. The model also predicts a bifurcation from transient to sustained release which may link local and global calcium signals in cells.

  20. Intestinal absorption and renal reabsorption of calcium throughout postnatal development.

    Science.gov (United States)

    Beggs, Megan R; Alexander, R Todd

    2017-04-01

    Calcium is vital for many physiological functions including bone mineralization. Postnatal deposition of calcium into bone is greatest in infancy and continues through childhood and adolescence until peek mineral density is reached in early adulthood. Thereafter, bone mineral density remains static until it eventually declines in later life. A positive calcium balance, i.e. more calcium absorbed than excreted, is crucial to bone deposition during growth and thus to peek bone mineral density. Dietary calcium is absorbed from the intestine into the blood. It is then filtered by the renal glomerulus and either reabsorbed by the tubule or excreted in the urine. Calcium can be (re)absorbed across intestinal and renal epithelia via both transcellular and paracellular pathways. Current evidence suggests that significant intestinal and renal calcium transport changes occur throughout development. However, the molecular details of these alterations are incompletely delineated. Here we first briefly review the current model of calcium transport in the intestine and renal tubule in the adult. Then, we describe what is known with regard to calcium handling through postnatal development, and how alterations may aid in mediating a positive calcium balance. The role of transcellular and paracellular calcium transport pathways and the contribution of specific intestinal and tubular segments vary with age. However, the current literature highlights knowledge gaps in how specifically intestinal and renal calcium (re)absorption occurs early in postnatal development. Future research should clarify the specific changes in calcium transport throughout early postnatal development including mediators of these alterations enabling appropriate bone mineralization. Impact statement This mini review outlines the current state of knowledge pertaining to the molecules and mechanisms maintaining a positive calcium balance throughout postnatal development. This process is essential to achieving