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Voltage-gated Calcium Channels (voltage-gated + calcium_channel)

Distribution by Scientific Domains

Life Sciences	68%
Medical Sciences	31%

Selected Abstracts

Cloning and characterization of voltage-gated calcium channel alpha1 subunits in Xenopus laevis during development

DEVELOPMENTAL DYNAMICS, Issue 11 2009
Brittany B. Lewis
Abstract Voltage-gated calcium channels play a critical role in regulating the Ca2+ activity that mediates many aspects of neural development, including neural induction, neurotransmitter phenotype specification, and neurite outgrowth. Using Xenopus laevis embryos, we describe the spatial and temporal expression patterns during development of the 10 pore-forming alpha1 subunits that define the channels' kinetic properties. In situ hybridization indicates that CaV1.2, CaV2.1, CaV2.2, and CaV3.2 are expressed during neurula stages throughout the neural tube. These, along with CaV1.3 and CaV2.3, beginning at early tail bud stages, and CaV3.1 at late tail bud stages, are detected in complex patterns within the brain and spinal cord through swimming tadpole stages. Additional expression of various alpha1 subunits was observed in the cranial ganglia, retina, olfactory epithelium, pineal gland, and heart. The unique expression patterns for the different alpha1 subunits suggests they are under precise spatial and temporal regulation and are serving specific functions during embryonic development. Developmental Dynamics 238:2891,2902, 2009. © 2009 Wiley-Liss, Inc. [source]

The effect of sevoflurane on glutamate release and uptake in rat cerebrocortical presynaptic terminals

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2002
M. L. Vinje
Background: Volatile anaesthetics exert their effect in the brain mainly by reducing synaptic excitability. Isoflurane abates excitation by reducing the release and increasing the uptake of transmitter glutamate into the presynaptic terminal. The exact molecular mechanisms exerting these effects, however, are not clear. Voltage-gated calcium channels have been proposed as the pharmacological target. The present study examines the effect of sevoflurane on synaptic glutamate release and free cytosolic calcium and the effect on high- and low-affinity uptake of L-glutamate using isolated presynaptic terminals prepared from rat cerebral cortex. Methods: Released glutamate was measured fluorometrically in a spectrophotometer as the fluorescence of NADPH and calcium as the fluorescence of fura-2. 4-aminopyridine was used to induce membrane depolarization. Glutamate uptake was measured in a series of different concentrations of L-glutamate corresponding to the high- and the low- affinity uptake systems adding a fixed concentration og radiolabelled glutamate. The labelling was measured by counting disintegrations per min in a ,-scintillation counter. Results: Sevoflurane reduced the calcium-dependent glutamate release in a dose-dependent manner as sevoflurane 1.5, 2.5 and 4.0% reduced the release by 58, 69 and 94%, respectively (P<0.05). Membrane depolarization induced an increase in free cytosolic calcium by 25%. Sevoflurane did not affect this increase. Neither the high- nor the low-affinity uptake transporter systems are affected by the anaesthetic. Conclusion: These results indicate that different volatile anaesthetics may act differently on the presynaptic terminal. The exact modes of action have to be further investigated. [source]

Cloning and characterization of voltage-gated calcium channel alpha1 subunits in Xenopus laevis during development

Identification of genes influencing skeletal phenotypes in congenic P/NP rats

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2010
Imranul Alam
Abstract We previously showed that alcohol-preferring (P) rats have higher bone density than alcohol-nonpreferring (NP) rats. Genetic mapping in P and NP rats identified a major quantitative trait locus (QTL) between 4q22 and 4q34 for alcohol preference. At the same location, several QTLs linked to bone density and structure were detected in Fischer 344 (F344) and Lewis (LEW) rats, suggesting that bone mass and strength genes might cosegregate with genes that regulate alcohol preference. The aim of this study was to identify the genes segregating for skeletal phenotypes in congenic P and NP rats. Transfer of the NP chromosome 4 QTL into the P background (P.NP) significantly decreased areal bone mineral density (aBMD) and volumetric bone mineral density (vBMD) at several skeletal sites, whereas transfer of the P chromosome 4 QTL into the NP background (NP.P) significantly increased bone mineral content (BMC) and aBMD in the same skeletal sites. Microarray analysis from the femurs using Affymetrix Rat Genome arrays revealed 53 genes that were differentially expressed among the rat strains with a false discovery rate (FDR) of less than 10%. Nine candidate genes were found to be strongly correlated (r2,>,0.50) with bone mass at multiple skeletal sites. The top three candidate genes, neuropeptide Y (Npy), , synuclein (Snca), and sepiapterin reductase (Spr), were confirmed using real-time quantitative PCR (qPCR). Ingenuity pathway analysis revealed relationships among the candidate genes related to bone metabolism involving ,-estradiol, interferon-,, and a voltage-gated calcium channel. We identified several candidate genes, including some novel genes on chromosome 4 segregating for skeletal phenotypes in reciprocal congenic P and NP rats. © 2010 American Society for Bone and Mineral Research [source]

Exclusion of 5 functional candidate genes for distal hereditary motor neuropathy type II (distal HMN II) linked to 12q24.3

ANNALS OF HUMAN GENETICS, Issue 6 2001
J. IROBI
Distal hereditary motor neuropathies (distal HMNs) are characterised by degeneration of anterior horn cells of the spinal cord resulting in muscle weakness and atrophy. Distal HMN type II is genetically linked to chromosome 12q24.3 and located within a 13 cM region flanked by markers D12S86 and D12S340. We previously excluded the human phospholipase A2 group 1B gene (PLA2G1B) as the disease causing gene. Here, we report the mutation analysis of five other candidate genes localised within the distal HMN II region: the cytoskeletal proteins paxillin (PXN) and restin (RSN); the acidic ribosomal phosphoprotein, large P0 subunit (RPLP0); a nucleoside diphosphate kinase (NME2B); and the , 3 subunit of the voltage-gated calcium channel (CACNB3). DNA sequencing of the coding regions was performed but no disease causing mutations could be identified, hence excluding these five genes for distal HMN type II. [source]

Pregabalin Exerts Oppositional Effects on Different Inhibitory Circuits in Human Motor Cortex: A Double-blind, Placebo-controlled Transcranial Magnetic Stimulation Study

EPILEPSIA, Issue 5 2006
Nicolas Lang
Summary:,Purpose: To explore acute effects of pregabalin (PGB) on human motor cortex excitability with transcranial magnetic stimulation (TMS). Methods: PGB, 600 mg/day, was orally administered in 19 healthy subjects twice daily in a randomized, double-blind, placebo-controlled crossover design. Several measures of motor cortex excitability were tested with single- and paired-pulse TMS. Results: Mean short-interval intracortical inhibition (SICI) was reduced after PGB (74 ± 7% of unconditioned response) compared with placebo (60 ± 6% of unconditioned response). In contrast, mean long-interval intracortical inhibition (LICI) was increased by PGB (26 ± 4% of unconditioned response) compared with placebo (45 ± 8% of unconditioned response), and mean cortical silent period (CSP) showed an increase from 139 ± 8 ms or 145 ± 8 ms after placebo to 162 ± 7 ms or 161 ± 10 ms after PGB. Motor thresholds, intracortical facilitation, and corticospinal excitability were unaffected. Conclusions: The observed excitability changes with oppositional effects on SICI and LICI or CSP suggest ,-aminobutyric acid (GABA)B -receptor activation. They are markedly distinct from those induced by gabapentin, although both PGB and gabapentin are thought to mediate their function by binding to the ,(2)-, subunit of voltage-gated calcium channels. Conversely, the TMS profile of PGB shows striking similarities with the pattern evoked by the GABA-reuptake inhibitor tiagabine. [source]

Synchrony of spontaneous calcium activity in mouse neocortex before synaptogenesis

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2007
Jean-Claude Platel
Abstract Spontaneous calcium activity can be detected in embryonic mouse cortical slices as fluorescence intensity variations, in the presence of a fluorescent calcium indicator. Current methods to detect and quantify these variations depend heavily on experimenters whose judgement may interfere with measurement. In the present work, we developed new software called CalSignal for automatic detection and tracking of cellular bodies and quantification of spontaneous calcium activity on time-series of confocal fluorescence images. Analysis of 28 neocortical slices revealed that 21.0% of detected cells displayed peaks of fluorescence corresponding to spontaneous activity, with a mean frequency of one peak per 4 min. This activity was blocked in the absence of extracellular calcium but was not modified after depletion of calcium stores with thapsigargin or blockade of voltage-gated calcium channels with Ni2+. Further, statistical analysis of calcium activity revealed concomitant activation of distant cells in 24 slices, and the existence of a significant network of synchrony based on such coactivations in 17 slices out of 28. These networks enclosed 84.3% of active cells, scattered throughout the neocortical wall (mean distance between cellular bodies, 111.7 µm). Finally, it was possible to identify specific cells which were synchronously active with more neighbouring cells than others. The identity of these nodal cells remains to be investigated to fully comprehend the role of spontaneous calcium activity, before synaptogenesis, in shaping cortical neurogenesis. [source]

,-Conotoxin CVIB differentially inhibits native and recombinant N- and P/Q-type calcium channels

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2007
Leonid Motin
Abstract ,-Conotoxins are routinely used as selective inhibitors of different classes of voltage-gated calcium channels (VGCCs) in excitable cells. In the present study, we examined the potent N-type VGCC antagonist ,-conotoxin CVID and non-selective N- and P/Q-type antagonist CVIB for their ability to block native VGCCs in rat dorsal root ganglion (DRG) neurons and recombinant VGCCs expressed in Xenopus oocytes. ,-Conotoxins CVID and CVIB inhibited depolarization-activated whole-cell VGCC currents in DRG neurons with pIC50 values of 8.12 ± 0.05 and 7.64 ± 0.08, respectively. Inhibition of Ba2+ currents in DRG neurons by CVID (, 66% of total) appeared to be irreversible for >,30 min washout, whereas Ba2+ currents exhibited rapid recovery from block by CVIB (, 80% within 3 min). The recoverable component of the Ba2+ current inhibited by CVIB was mediated by the N-type VGCC, whereas the irreversibly blocked current (, 22% of total) was attributable to P/Q-type VGCCs. ,-Conotoxin CVIB reversibly inhibited Ba2+ currents mediated by N- (CaV2.2) and P/Q- (CaV2.1), but not R- (CaV2.3) type VGCCs expressed in Xenopus oocytes. The ,2,1 auxiliary subunit co-expressed with CaV2.2 and CaV2.1 reduced the sensitivity of VGCCs to CVIB but had no effect on reversibility of block. Determination of the NMR structure of CVIB identified structural differences to CVID that may underlie differences in selectivity of these closely related conotoxins. ,-Conotoxins CVIB and CVID may be useful as antagonists of N- and P/Q-type VGCCs, particularly in sensory neurons involved in processing primary nociceptive information. [source]

Calcium signaling in invertebrate glial cells

GLIA, Issue 7 2006
Christian Lohr
Abstract Calcium signaling studies in invertebrate glial cells have been performed mainly in the nervous systems of the medicinal leech (Hirudo medicinalis) and the sphinx moth Manduca sexta. The main advantages of studing glial cells in invertebrate nervous systems are the large size of invertebrate glial cells and their easy accessibility for optical and electrophysiological recordings. Glial cells in both insects and annelids express voltage-gated calcium channels and, in the case of leech glial cells, calcium-permeable neurotransmitter receptors, which allow calcium influx as one major source for cytosolic calcium transients. Calcium release from intracellular stores can be induced by metabotropic receptor activation in leech glial cells, but appears to play a minor role in calcium signaling. In glial cells of the antennal lobe of Manduca, voltage-gated calcium signaling changes during postembryonic development and is essential for the migration of the glial cells, a key step in axon guidance and in stabilization of the glomerular structures that are characteristic of primary olfactory centers. © 2006 Wiley-Liss, Inc. [source]

Blockage of voltage-gated calcium signaling impairs migration of glial cells in vivo

GLIA, Issue 3 2005
Christian Lohr
Abstract Migration of glial cells is an essential step in the development of the antennal lobe, the primary olfactory center of insects, to establish well-defined borders between olfactory glomeruli required for odor discrimination. In the present study, we used two-photon microscopy to visualize calcium signaling in developing antennal lobe glial cells of the sphinx moth Manduca sexta. We found a correlation between the upregulation of functional voltage-gated calcium channels and the onset of glial cell migration. In addition, glial cells migrating into the center of the antennal lobe express larger voltage-gated calcium transients than glial cells that remain at the periphery. Migration behavior and calcium signaling of glial cells in vivo were manipulated either by deafferentation, by injection of the calcium channel blockers diltiazem, verapamil, and flunarizine, or by injection of the calcium chelators BAPTA-AM and Fluo-4-AM. In deafferented antennal lobes, glial cells failed to express functional voltage-gated calcium channels and did not migrate. Calcium channel blockage or reducing glial calcium signals by calcium chelators prevented glial cell migration and resulted in antennal lobes lacking glial borders around glomeruli, indicating that voltage-gated calcium signaling is required for the migration of antennal lobe glial cells and the development of mature olfactory glomeruli. © 2005 Wiley-Liss, Inc. [source]

KP4 fungal toxin inhibits growth in Ustilago maydis by blocking calcium uptake

MOLECULAR MICROBIOLOGY, Issue 4 2001
Matthew J. Gage
KP4 is a virally encoded fungal toxin secreted by the P4 killer strain of Ustilago maydis. From our previous structural studies , it seemed unlikely that KP4 acts by forming channels in the target cell membrane. Instead, KP4 was proposed to act by blocking fungal calcium channels, as KP4 was shown to inhibit voltage-gated calcium channels in rat neuronal cells, and its effects on fungal cells were abrogated by exogenously added calcium. Here, we extend these studies and demonstrate that KP4 acts in a reversible manner on the cell membrane and does not kill the cells, but rather inhibits cell division. This action is mimicked by EGTA and is abrogated specifically by low concentrations of calcium or non-specifically by high ionic strength buffers. We also demonstrate that KP4 affects 45Ca uptake in U. maydis. Finally, we show that cAMP and a cAMP analogue, N 6,2,-O-dibutyryladenosine 3,:5,-cyclic monophosphate, both abrogate KP4 effects. These results suggest that KP4 may inhibit cell growth and division by blocking calcium-regulated signal transduction pathways. [source]

Regulation of Kv channel expression and neuronal excitability in rat medial nucleus of the trapezoid body maintained in organotypic culture

THE JOURNAL OF PHYSIOLOGY, Issue 9 2010
Huaxia Tong
Principal neurons of the medial nucleus of the trapezoid body (MNTB) express a spectrum of voltage-dependent K+ conductances mediated by Kv1,Kv4 channels, which shape action potential (AP) firing and regulate intrinsic excitability. Postsynaptic factors influencing expression of Kv channels were explored using organotypic cultures of brainstem prepared from P9,P12 rats and maintained in either low (5 mm, low-K) or high (25 mm, high-K) [K+]o medium. Whole cell patch-clamp recordings were made after 7,28 days in vitro. MNTB neurons cultured in high-K medium maintained a single AP firing phenotype, while low-K cultures had smaller K+ currents, enhanced excitability and fired multiple APs. The calyx of Held inputs degenerated within 3 days in culture, having lost their major afferent input; this preparation of calyx-free MNTB neurons allowed the effects of postsynaptic depolarisation to be studied with minimal synaptic activity. The depolarization caused by the high-K aCSF only transiently increased spontaneous AP firing (<2 min) and did not measurably increase synaptic activity. Chronic depolarization in high-K cultures raised basal levels of [Ca2+]i, increased Kv3 currents and shortened AP half-widths. These events relied on raised [Ca2+]i, mediated by influx through voltage-gated calcium channels (VGCCs) and release from intracellular stores, causing an increase in cAMP-response element binding protein (CREB) phosphorylation. Block of VGCCs or of CREB function suppressed Kv3 currents, increased AP duration, and reduced Kv3.3 and c- fos expression. Real-time PCR revealed higher Kv3.3 and Kv1.1 mRNA in high-K compared to low-K cultures, although the increased Kv1.1 mRNA was mediated by a CREB-independent mechanism. We conclude that Kv channel expression and hence the intrinsic membrane properties of MNTB neurons are homeostatically regulated by [Ca2+]i -dependent mechanisms and influenced by sustained depolarization of the resting membrane potential. [source]

Acute exposure to low-level CW and GSM-modulated 900 MHz radiofrequency does not affect Ba2+ currents through voltage-gated calcium channels in rat cortical neurons

BIOELECTROMAGNETICS, Issue 8 2007
Daniela Platano
Abstract We have studied the non-thermal effects of radiofrequency (RF) electromagnetic fields (EMFs) on Ba2+ currents () through voltage-gated calcium channels (VGCC), recorded in primary cultures of rat cortical neurons using the patch-clamp technique. To assess whether low-level acute RF field exposure could modify the amplitude and/or the voltage-dependence of , Petri dishes containing cultured neurons were exposed for 1,3 periods of 90 s to 900 MHz RF-EMF continuous wave (CW) or amplitude-modulated according to global system mobile communication standard (GSM) during whole-cell recording. The specific absorption rates (SARs) were 2 W/kg for CW and 2 W/kg (time average value) for GSM-modulated signals, respectively. The results obtained indicate that single or multiple acute exposures to either CW or GSM-modulated 900 MHz RF-EMFs do not significantly alter the current amplitude or the current,voltage relationship of , through VGCC. Bioelectromagnetics 28:599,607, 2007. © 2007 Wiley-Liss, Inc. [source]

N -Acyl amino acids and N -acyl neurotransmitter conjugates: neuromodulators and probes for new drug targets

BRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2010
Mark Connor
The myriad functions of lipids as signalling molecules is one of the most interesting fields in contemporary pharmacology, with a host of compounds recognized as mediators of communication within and between cells. The N -acyl conjugates of amino acids and neurotransmitters (NAANs) have recently come to prominence because of their potential roles in the nervous system, vasculature and the immune system. NAAN are compounds such as glycine, GABA or dopamine conjugated with long chain fatty acids. More than 70 endogenous NAAN have been reported although their physiological role remains uncertain, with various NAAN interacting with a low affinity at G protein coupled receptors (GPCR) and ion channels. Regardless of their potential physiological function, NAAN are of great interest to pharmacologists because of their potential as flexible tools to probe new sites on GPCRs, transporters and ion channels. NAANs are amphipathic molecules, with a wide variety of potential fatty acid and headgroup moieties, a combination which provides a rich source of potential ligands engaging novel binding sites and mechanisms for modulation of membrane proteins such as GPCRs, ion channels and transporters. The unique actions of subsets of NAAN on voltage-gated calcium channels and glycine transporters indicate that the wide variety of NAAN may provide a readily exploitable resource for defining new pharmacological targets. Investigation of the physiological roles and pharmacological potential of these simple lipid conjugates is in its infancy, and we believe that there is much to be learnt from their careful study. [source]

Clinical aspects of neuromuscular transmission disorders

ACTA NEUROLOGICA SCANDINAVICA, Issue 2006
Amelia Evoli
Autoimmune disorders of neuromuscular transmission are caused by antibodies (abs) directed against membrane proteins at the motor end-plate. Myasthenia gravis (MG) is due, in most cases, to abs against the nicotinic acetylcholine receptor (AChR). Anti-AChR-positive MG actually includes different disease entities: weakness can be confined to extrinsic ocular muscles or can be generalized; patients with generalized MG (G-MG) can be subdivided on the basis of age of onset, HLA association and thymic pathology. About 15% of G-MG patients are anti-AChR-negative; in a proportion of these cases serum abs against the muscle- specific kinase (MuSK) are found. Anti-MuSK-positive MG is characterized by predominant involvement of bulbar muscles and very low frequency of thymic pathology. The Lambert-Eaton myasthenic syndrome (LEMS) is caused by abs against voltage-gated calcium channels at nerve terminal. LEMS is characterized by muscle weakness and autonomic disturbances and it is paraneoplastic in over 50% of the cases. In neuromyotonia and cramp-fasciculation syndrome, that are thought to be due to anti-voltage-gated potassium channel abs, signs of peripheral nerve hyperexcitability can be associated with CNS features. [source]