Molecular Mimicking of Phosphorylation at S1928 and S1700-T1704 Confers Modified Surface Traffic Properties to CaV1.2 Voltage Gated Calcium Channels in Cultured Hippocampal Neurons

1. Cultured hippocampal neurons were recorded with a patch pipette containing 100 microM of the calcium indicator Fluo-3, and one of their dendrites, carrying dendritic spines, was visualized with a x100, 1.3-numerical aperture oil objective. Calcium spikes evoked by depolarizing the somata and changes in free dendrite and spine calcium concentrations ([Ca]d and [Ca]s, respectively) were monitored with a cooled charge-coupled device (CCD) camera, acquiring images at a rate of 17-20 ms per frame. In the majority of spine-dendrite pairs, [Ca]s rose faster and to a higher level than the adjacent [Ca]d. Likewise, topical application of glutamate evoked a faster and larger change in [Ca]s than in [Ca]d. The rise of intracellular calcium concentration in response to a depolarizing current pulse, but not in response to glutamate, was reduced in the presence of the calcium antagonist verapamil in both dendrites and spines. It is suggested that dendritic spines possess voltage-gated calcium channels.

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Distribution of CaV1.2 L-type voltage-gated calcium channels and β adrenergic receptors signaling complexes in cultured hippocampal neurons

Intrinsic Activity ◽

10.25006/ia.1.s1-a1.51 ◽

2013 ◽

Vol 1 (Suppl. 1) ◽

pp. A1.51

Author(s):

Claudia Ramprecht

Keyword(s):

Calcium Channels ◽

Adrenergic Receptors ◽

Hippocampal Neurons ◽

Voltage Gated ◽

Voltage Gated Calcium Channels ◽

Β Adrenergic Receptors ◽

Cultured Hippocampal Neurons

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

Acta Pharmacologica Sinica ◽

10.1038/aps.2011.181 ◽

2012 ◽

Vol 33 (4) ◽

pp. 438-444 ◽

Cited By ~ 26

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

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

International Journal of Molecular Sciences ◽

10.3390/ijms221910342 ◽

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.

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