scholarly journals Voltage-gated calcium channels trigger spontaneous glutamate release via nanodomain coupling

2020 ◽  
Author(s):  
Byoung Ju Lee ◽  
Che Ho Yang ◽  
Seung Yeon Lee ◽  
Suk-Ho Lee ◽  
Yujin Kim ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Spontaneous Release ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Key Factor ◽  
Mepsc Frequency ◽  
Tightly Coupled

ABSTRACTNeurotransmitter release occurs either synchronously to action potentials or spontaneously, yet whether molecular machineries underlying evoked and spontaneous release are identical, especially whether voltage-gated Ca2+ channels (VGCCs) can trigger spontaneous events has been in debate. To elucidate this issue, we characterized Ca2+ dependency of miniature excitatory postsynaptic currents (mEPSCs) in autaptic cultured hippocampal neurons. We found that 58 % mEPSC frequency was dependent on extracellular Ca2+([Ca2+]o), and Ca2+cooperativity of spontaneous release was comparable to that of evoked release. Moreover, most (> 90 %) of [Ca2+]o-dependent mEPSCs was attributable to VGCCs. Coupling distance between VGCCs and Ca2+ sensors was estimated as tight for both spontaneous and evoked release (~22 nm). In hippocampal slices, VGCC-dependence on spontaneous release was also observed, but to a different extent, at different areas and ages. At the calyx of Held synapses, mEPSCs showed VGCC-dependence in type 1 mature synapses where VGCCs and Ca2+ sensors are tightly coupled, but not in immature synapses. These data strongly suggest that the distance between VGCCs and Ca2+ sensors is the key factor to determine VGCC dependence of spontaneous release.

scholarly journals Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels in cultured rat hippocampal neurons

2012 ◽  
Vol 33 (4) ◽  
pp. 438-444 ◽  
Author(s):  
Zhi-ying Lin ◽  
Li-min Chen ◽  
Jing Zhang ◽  
Xiao-dong Pan ◽  
Yuan-gui Zhu ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Hippocampal Neurons ◽  
Ginsenoside Rb1 ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels

scholarly journals Role of L-Type Voltage-Gated Calcium Channels in Epileptiform Activity of Neurons

2021 ◽  
Vol 22 (19) ◽  
pp. 10342
Author(s):  
Denis P. Laryushkin ◽  
Sergei A. Maiorov ◽  
Valery P. Zinchenko ◽  
Sergei G. Gaidin ◽  
Artem M. Kosenkov
Keyword(s):  
Calcium Channels ◽  
Hippocampal Neurons ◽  
Epileptiform Activity ◽  
Gaba A ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Effective Doses ◽  
High Doses ◽  
Paroxysmal Depolarization Shift

Epileptic discharges manifest in individual neurons as abnormal membrane potential fluctuations called paroxysmal depolarization shift (PDS). PDSs can combine into clusters that are accompanied by synchronous oscillations of the intracellular Ca2+ concentration ([Ca2+]i) in neurons. Here, we investigate the contribution of L-type voltage-gated calcium channels (VGCC) to epileptiform activity induced in cultured hippocampal neurons by GABA(A)R antagonist, bicuculline. Using KCl-induced depolarization, we determined the optimal effective doses of the blockers. Dihydropyridines (nifedipine and isradipine) at concentrations ≤ 10 μM demonstrate greater selectivity than the blockers from other groups (phenylalkylamines and benzothiazepines). However, high doses of dihydropyridines evoke an irreversible increase in [Ca2+]i in neurons and astrocytes. In turn, verapamil and diltiazem selectively block L-type VGCC in the range of 1–10 μM, whereas high doses of these drugs block other types of VGCC. We show that L-type VGCC blockade decreases the half-width and amplitude of bicuculline-induced [Ca2+]i oscillations. We also observe a decrease in the number of PDSs in a cluster and cluster duration. However, the pattern of individual PDSs and the frequency of the cluster occurrence change insignificantly. Thus, our results demonstrate that L-type VGCC contributes to maintaining the required [Ca2+]i level during oscillations, which appears to determine the number of PDSs in the cluster.

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.

Early anoxia-induced vesicular glutamate release results from mobilization of calcium from intracellular stores

1993 ◽  
Vol 70 (1) ◽  
pp. 1-7 ◽  
Author(s):  
A. N. Katchman ◽  
N. Hershkowitz
Keyword(s):  
Calcium Influx ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Calcium Currents ◽  
Patch Clamp Recording ◽  
Ca1 Neurons ◽  
Whole Cell Patch Clamp ◽  
Mepsc Frequency ◽  
Synaptic Changes

1. The cause of the increased frequency of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) resulting from anoxia was investigated in CA1 neurons of the in vitro rat hippocampal slice. These neurons were examined by whole-cell patch-clamp recording, and hypoxia was induced by switching the perfusion of the slice from oxygenated artificial cerebral spinal fluid (ACSF) to ACSF saturated with 95% N2-5% O2. Except where noted, experiments were carried out in ACSF containing 1 microM tetrodotoxin (TTX). 2. Although anoxia resulted in a significant increase in the frequency of mEPSCs, the amplitude, rise time, and half-decay time of the mEPSCs were unchanged. This increase in frequency indicates that there is a change in presynaptic neurotransmitter release mechanisms, probably an increase in calcium concentration, soon after the onset of anoxia. The unchanged kinetics and amplitude of the mEPSCs indicate that anoxic-induced synaptic changes are not a result of changes in the postsynaptic glutamate receptor. 3. When hippocampal slices were exposed to anoxic conditions in ACSF with calcium excluded, an increase in mEPSC frequency equal to that in normal ACSF was observed. When 0.2 mM of CdCl2 was added to the zero-calcium ACSF, anoxia still resulted in increases in mEPSC frequency equal to those of normal ACSF. It is therefore concluded that the anoxia-induced increase in mEPSC frequency does not result from an increase in a transmembrane calcium influx. The zero-calcium plus 0.2 mM CdCl2 ACSF solution completely abolished orthodromically elicited synaptic potential (in the absence of TTX), indicating that calcium currents that mediate normal orthodromic transmitter release were completely abolished in the latter experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Do voltage-gated calcium channel α2δ subunits require proteolytic processing into α2 and δ to be functional?

2006 ◽  
Vol 34 (5) ◽  
pp. 894-898 ◽  
Author(s):  
L. Douglas ◽  
A. Davies ◽  
J. Wratten ◽  
A.C. Dolphin
Keyword(s):  
Calcium Channel ◽  
Disulfide Bonds ◽  
Proteolytic Processing ◽  
Future Research ◽  
Temperature Sensitive ◽  
Channel Trafficking ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Open Question

The accessory α2δ subunits of voltage-gated calcium channels are type 1 transmembrane proteins that are highly glycosylated and possess multiple disulfide bonds. From studies of the topology and processing of skeletal-muscle α2δ-1, it has been shown to be post-translationally cleaved into an α2 and a δ subunit, which remain disulfide-bonded. In the present study, we have examined the processing of α2δ-2 subunits when stably or transiently expressed, in tsA (temperature-sensitive A)-201, Cos-7 and NG108-15 cells, and compared it with that observed in the cerebellum. Despite showing full functionality and being expressed on the plasma membrane, the vast majority of heterologously expressed α2δ-2 is not cleaved into α2-2 and δ-2, unlike endogenous α2δ-2 in the cerebellum. It remains an open question for future research whether α2δ-2 is functional in its calcium channel trafficking role in its proteolytically cleaved or non-cleaved state.

scholarly journals The Specific Effects of OD-1, a Peptide Activator, on Voltage-Gated Sodium Current and Seizure Susceptibility

2020 ◽  
Vol 21 (21) ◽  
pp. 8254
Author(s):  
Ming-Chi Lai ◽  
Sheng-Nan Wu ◽  
Chin-Wei Huang
Keyword(s):  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Sodium Current ◽  
Hippocampal Slices ◽  
Inactivation Curve ◽  
Voltage Gated ◽  
Epileptiform Discharges ◽  
State Dependent ◽  
Na Currents

OD-1, a scorpion toxin, has been previously recognized as an activator of voltage-gated Na+ currents. To what extent this agent can alter hippocampal neuronal Na+ currents and network excitability and how it can be applied to neuronal hyperexcitability research remains unclear. With the aid of patch-clamp technology, it was revealed that, in mHippoE-14 hippocampal neurons, OD-1 produced a concentration-, time-, and state-dependent rise in the peak amplitude of INa. It shifted the INa inactivation curve to a less negative potential and increased the frequency of spontaneous action currents. Further characterization of neuronal excitability revealed higher excitability in the hippocampal slices treated with OD-1 as compared with the control slices. A stereotaxic intrahippocampal injection of OD-1 generated a significantly higher frequency of spontaneous seizures and epileptiform discharges compared with intraperitoneal injection of lithium-pilocarpine- or kainic acid-induced epilepsy, with comparable pathological changes. Carbamazepine significantly attenuated OD-1 induced seizures and epileptiform discharges. The OD-1-mediated modifications of INa altered the electrical activity of neurons in vivo and OD-1 could potentially serve as a novel seizure and excitotoxicity model.

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