scholarly journals Ciliary Ca2+ pumps regulate intraciliary Ca2+ from the action potential and may co-localize with ciliary voltage-gated Ca2+ channels

2021 ◽  
Vol 224 (9) ◽  
Author(s):  
Junji Yano ◽  
Russell Wells ◽  
Ying-Wai Lam ◽  
Judith L. Van Houten
Keyword(s):  
Action Potential ◽  
Calcium Ions ◽  
Power Stroke ◽  
Paramecium Tetraurelia ◽  
Density Fractions ◽  
Voltage Gated ◽  
Calcium Pumps ◽  
Voltage Gated Calcium Channels ◽  
The Family ◽  
Ca2 Channels

ABSTRACT Calcium ions (Ca2+) entering cilia through the ciliary voltage-gated calcium channels (CaV) during the action potential causes reversal of the ciliary power stroke and backward swimming in Paramecium tetraurelia. How calcium is returned to the resting level is not yet clear. Our focus is on calcium pumps as a possible mechanism. There are 23 P. tetraurelia genes for calcium pumps that are members of the family of plasma membrane Ca2+ ATPases (PMCAs). They have domains homologous to those found in mammalian PMCAs. Of the 13 pump proteins previously identified in cilia, ptPMCA2a and ptPMCA2b are most abundant in the cilia. We used RNAi to examine which PMCA might be involved in regulating intraciliary Ca2+ after the action potential. RNAi for only ptPMCA2a and ptPMCA2b causes cells to significantly prolong their backward swimming, which indicates that Ca2+ extrusion in the cilia is impaired when these PMCAs are depleted. We used immunoprecipitations (IP) to find that ptPMCA2a and ptPMCA2b are co-immunoprecipitated with the CaV channel α1 subunits that are found only in the cilia. We used iodixanol (OptiPrep) density gradients to show that ptPMCA2a and ptPMCA2b and CaV1c are found in the same density fractions. These results suggest that ptPMCA2a and ptPMCA2b are located in the proximity of ciliary CaV channels.

Voltage gating of ion channels

1994 ◽  
Vol 27 (1) ◽  
pp. 1-40 ◽  
Author(s):  
F. J. Sigworth
Keyword(s):  
Ion Channels ◽  
Action Potential ◽  
Sodium Channels ◽  
Calcium Ions ◽  
Neurotransmitter Release ◽  
Voltage Gating ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Voltage Gated Sodium Channels ◽  
Voltage Gated Ion Channels

Voltage-gated ion channels are membrane proteins that play a central role in the propagation and transduction of cellular signals (Hille, 1992). Calcium ions entering cells through voltage-gated calcium channels serve as the trigger for neurotransmitter release, muscle contraction, and the release of hormones. Voltage-gated sodium channels initiate the nerve action potential and provide for its rapid propagation because the ion fluxes through these channels regeneratively cause more channels to open.

Inhibition of Dendritic Calcium Influx by Activation of G-Protein–Coupled Receptors in the Hippocampus

1997 ◽  
Vol 78 (6) ◽  
pp. 3484-3488 ◽  
Author(s):  
Huanmian Chen ◽  
Nevin A. Lambert
Keyword(s):  
Calcium Channels ◽  
Action Potential ◽  
G Protein ◽  
Pyramidal Neuron ◽  
Action Potentials ◽  
Calcium Influx ◽  
G Protein Coupled Receptors ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
G Protein Coupled

Chen, Huanmian and Nevin A. Lambert. Inhibition of dendritic calcium influx by activation of G-protein–coupled receptors in the hippocampus. J. Neurophysiol. 78: 3484–3488, 1997. Gi proteins inhibit voltage-gated calcium channels and activate inwardly rectifying K+ channels in hippocampal pyramidal neurons. The effect of activation of G-protein–coupled receptors on action potential-evoked calcium influx was examined in pyramidal neuron dendrites with optical and extracellular voltage recording. We tested the hypotheses that 1) activation of these receptors would inhibit calcium channels in dendrites; 2) hyperpolarization resulting from K+ channel activation would deinactivate low-threshold, T-type calcium channels on dendrites, increasing calcium influx mediated by these channels; and 3) activation of these receptors would inhibit propagation of action potentials into dendrites, and thus indirectly decrease calcium influx. Activation of adenosine receptors, which couple to Gi proteins, inhibited calcium influx in cell bodies and proximal dendrites without inhibiting action-potential propagation into the proximal dendrites. Inhibition of dendritic calcium influx was not changed in the presence of 50 μM nickel, which preferentially blocks T-type channels, suggesting influx through these channels is not increased by activation of G-proteins. Adenosine inhibited propagation of action potentials into the distal branches of pyramidal neuron dendrites, leading to a three- to fourfold greater inhibition of calcium influx in the distal dendrites than in the soma or proximal dendrites. These results suggest that voltage-gated calcium channels are inhibited in pyramidal neuron dendrites, as they are in cell bodies and terminals and thatG-protein–mediated inhibition of action-potential propagation can contribute substantially to inhibition of dendritic calcium influx.

scholarly journals Voltage-gated calcium channels are not affected by the novel anti-epileptic drug lacosamide

2011 ◽  
Vol 2 (1) ◽  
Author(s):  
Yuying Wang ◽  
Rajesh Khanna
Keyword(s):  
Hippocampal Neurons ◽  
Neuronal Cell ◽  
Axonal Guidance ◽  
The Novel ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Voltage Gated Sodium Channels ◽  
Anti Epileptic Drug ◽  
Mediator Protein ◽  
Ca2 Channels

AbstractThe novel anti-epileptic drug lacosamide targets two proteins — voltage-gated sodium channels and collapsin response mediator protein 2 (CRMP-2) — suggesting dual modes of action for lacosamide. We recently identified the neurite outgrowth and axonal guidance protein CRMP-2 as a novel partner and regulator of the presynaptic N-type voltage-gated Ca2+ channel (CaV2.2) [Brittain et al., J. Biol. Chem. 284: 31375–31390 (2009)]. Here we examined the effects of lacosamide on voltage-gated Ba2+ channels. Lacosamide did not affect Ba2+ currents via N- and P/Q- channels in rat hippocampal neurons or L-type Ca2+ channels in a mouse CNS neuronal cell line, respectively. N-type Ba2+ currents, augmented by CRMP-2 expression, were also unaffected by acute or chronic lacosamide exposure. These results establish that the anti-epileptic mode of action of lacosamide does not involve these voltage-gated Ca2+ channels.

scholarly journals A homolog of mammalian, voltage-gated calcium channels mediates yeast pheromone-stimulated Ca2+ uptake and exacerbates the cdc1(Ts) growth defect.

1997 ◽  
Vol 17 (11) ◽  
pp. 6339-6347 ◽  
Author(s):  
M Paidhungat ◽  
S Garrett
Keyword(s):  
Sequence Similarity ◽  
Growth Defect ◽  
Temperature Sensitive ◽  
Mating Pheromone ◽  
Yeast Saccharomyces Cerevisiae ◽  
Significant Sequence Similarity ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Higher Eukaryotes ◽  
Ca2 Channels

Previous studies attributed the yeast (Saccharomyces cerevisiae) cdc1(Ts) growth defect to loss of an Mn2+-dependent function. In this report we show that cdc1(Ts) temperature-sensitive growth is also associated with an increase in cytosolic Ca2+. We identified two recessive suppressors of the cdc1(Ts) temperature-sensitive growth which block Ca2+ uptake and accumulation, suggesting that cytosolic Ca2+ exacerbates or is responsible for the cdc1(Ts) growth defect. One of the cdc1(Ts) suppressors is identical to a gene, MID1, recently implicated in mating pheromone-stimulated Ca2+ uptake. The gene (CCH1) corresponding to the second suppressor encodes a protein that bears significant sequence similarity to the pore-forming subunit (alpha1) of plasma membrane, voltage-gated Ca2+ channels from higher eukaryotes. Strains lacking Mid1 or Cch1 protein exhibit a defect in pheromone-induced Ca2+ uptake and consequently lose viability upon mating arrest. The mid1delta and cch1delta mutants also display reduced tolerance to monovalent cations such as Li+, suggesting a role for Ca2+ uptake in the calcineurin-dependent ion stress response. Finally, mid1delta cch1delta double mutants are, by both physiological and genetic criteria, identical to single mutants. These and other results suggest Mid1 and Cch1 are components of a yeast Ca2+ channel that may mediate Ca2+ uptake in response to mating pheromone, salt stress, and Mn2+ depletion.

scholarly journals Activity-dependent regulation of T-type calcium channels by submembrane calcium ions

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Magali Cazade ◽  
Isabelle Bidaud ◽  
Philippe Lory ◽  
Jean Chemin
Keyword(s):  
Calcium Ions ◽  
Large Decrease ◽  
Channel Activity ◽  
Ionotropic Receptors ◽  
Voltage Gated ◽  
Dependent Inactivation ◽  
Steady State Inactivation ◽  
Activity Dependent ◽  
Hyperpolarizing Shift ◽  
Ca2 Channels

Voltage-gated Ca2+ channels are involved in numerous physiological functions and various mechanisms finely tune their activity, including the Ca2+ ion itself. This is well exemplified by the Ca2+-dependent inactivation of L-type Ca2+ channels, whose alteration contributes to the dramatic disease Timothy Syndrome. For T-type Ca2+ channels, a long-held view is that they are not regulated by intracellular Ca2+. Here we challenge this notion by using dedicated electrophysiological protocols on both native and expressed T-type Ca2+ channels. We demonstrate that a rise in submembrane Ca2+ induces a large decrease in T-type current amplitude due to a hyperpolarizing shift in the steady-state inactivation. Activation of most representative Ca2+-permeable ionotropic receptors similarly regulate T-type current properties. Altogether, our data clearly establish that Ca2+ entry exerts a feedback control on T-type channel activity, by modulating the channel availability, a mechanism that critically links cellular properties of T-type Ca2+ channels to their physiological roles.

Dependency of hypoxic chemotransduction in cat carotid body on voltage-gated calcium channels

1991 ◽  
Vol 71 (3) ◽  
pp. 1062-1069 ◽  
Author(s):  
M. Shirahata ◽  
R. S. Fitzgerald
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Intracellular Calcium ◽  
Carotid Body ◽  
Calcium Ions ◽  
Extracellular Calcium ◽  
Bay K 8644 ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Selective Perfusion

The hypothesis that the entry of extracellular calcium ions into some compartment, quite possibly the type I cells, through voltage-gated calcium channels (VGCC) is essential for hypoxic chemotransduction in the cat carotid body was tested using an in situ perfusion technique. The neural output of the carotid body of anesthetized, paralyzed, and artificially ventilated cats in response to perfusions with Krebs-Ringer bicarbonate solution (KRB), calcium-free KRB, KRB containing calcium channel blockers, or KRB containing BAY K 8644 was recorded. Selective perfusion of the carotid body with hypoxic calcium-free KRB significantly decreased carotid chemoreceptor activity, suggesting that extracellular calcium is essential for hypoxic chemotransduction. Selective perfusion of the carotid body with hypoxic KRB containing verapamil (10–100 microM), diltiazem (10–100 microM), or nifedipine (10–100 microM) dose dependently attenuated the increase in chemoreceptor activity produced by hypoxia, suggesting that VGCC need to be activated for hypoxic chemotransduction. The carotid body response to hyperoxic KRB containing the calcium channel agonist BAY K 8644 (10 microM) was 267 +/- 87% of hyperoxic control KRB, suggesting that an enhanced influx of calcium ions through VGCC stimulates carotid chemoreceptor activity. Selective perfusion of the carotid body with severely hypoxic KRB containing BAY K 8644 did not increase chemoreceptor activity above that produced by severe hypoxia alone. This suggests that severe hypoxia increases intracellular calcium in some compartment of the carotid body to achieve stimulatory maximum response and that further increase in intracellular calcium does not produce further elevation of neural activity.(ABSTRACT TRUNCATED AT 250 WORDS)

A dihydropyridine-sensitive T-type Ca2+ current is the main Ca2+ current carrier in mouse primary spermatocytes

1996 ◽  
Vol 271 (5) ◽  
pp. C1583-C1593 ◽  
Author(s):  
C. M. Santi ◽  
A. Darszon ◽  
A. Hernandez-Cruz
Keyword(s):  
Germ Cells ◽  
Acrosome Reaction ◽  
Significant Inhibition ◽  
Mature Sperm ◽  
Sperm Cells ◽  
Meiotic Cell ◽  
Male Germ Cells ◽  
Voltage Gated ◽  
The Family ◽  
Ca2 Channels

Ca2+ entry through Ca2+ channels is likely to play an important role in the differentiation of male germ cells as well as in fertilization by mature sperm. Here we present a detailed analysis of Ca2+ currents expressed in acutely dissociated mouse primary spermatocytes. Patch-clamp recordings demonstrated that the only voltage-gated Ca2+ channels present belong to the family of T-type Ca2+ currents. Accordingly, Ni2+ (200 microM) and amiloride (500 microM) reduced current amplitude by 75 and 62%, respectively. To our knowledge, this is the first report of a system where T-type Ca2+ channels are expressed in isolation. Unexpectedly, 5 and 10 microM nifedipine also reduced peak currents by 38 and 53%, respectively significant inhibition of the Ca2+ current occurred at concentrations as low as 2 microM. Because mature sperm cells are unable to synthesize new proteins, these Ca2+ channels are also likely to be present in these cells, where they may contribute to the Ca2+ influx required to trigger the acrosome reaction. This notion is supported by the fact that concentrations of Ni2+ and nifedipine, which block these Ca2+ currents, also inhibit the acrosome reaction. Because these channels represent the primary pathway for voltage-gated Ca2+ entry in mouse spermatocytes, they may also participate in regulating meiotic cell division and sperm differentiation.

scholarly journals Calmodulin regulation (calmodulation) of voltage-gated calcium channels

2014 ◽  
Vol 143 (6) ◽  
pp. 679-692 ◽  
Author(s):  
Manu Ben-Johny ◽  
David T. Yue
Keyword(s):  
Ion Channel ◽  
Molecular Basis ◽  
Ion Channel Regulation ◽  
Therapeutic Implications ◽  
Voltage Gated ◽  
Channel Regulation ◽  
Voltage Gated Calcium Channels ◽  
The Family ◽  
Biological Insight ◽  
Recent Developments

Calmodulin regulation (calmodulation) of the family of voltage-gated CaV1-2 channels comprises a prominent prototype for ion channel regulation, remarkable for its powerful Ca2+ sensing capabilities, deep in elegant mechanistic lessons, and rich in biological and therapeutic implications. This field thereby resides squarely at the epicenter of Ca2+ signaling biology, ion channel biophysics, and therapeutic advance. This review summarizes the historical development of ideas in this field, the scope and richly patterned organization of Ca2+ feedback behaviors encompassed by this system, and the long-standing challenges and recent developments in discerning a molecular basis for calmodulation. We conclude by highlighting the considerable synergy between mechanism, biological insight, and promising therapeutics.

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