NMDA receptor agonists selectively block N-type calcium channels in hippocampal neurons

Natalya I. Chernevskaya, Alexander Obukhov, Oleg A. Krishtal

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

THE modulation of voltage-dependent calcium channels by various neurotransmitters has been demonstrated in many neurons1-4. Because of the critical role of Ca2+ in transmitter release and, more generally, in transmembrane signalling, this modulation has important functional implications. Hippocampal neurons possess low-threshold (T-type) Ca2+ channels and both L- and N-type high voltage-activated Ca2+ channels.5-7 N-type Ca2+ channels are blocked selectively by ω-conotoxin8,9 and adenosine10,11. These substances both block excitatory synaptic transmission in the hippocampus12-13, whereas dihydropyridines, which selectively block L-type channels14, are ineffective12. Excitatory synaptic transmission in the hippocampus displays a number of plasticity phenomena that are initiated by Ca2+ entry through ionic channels operated by N-methyl-D-aspartate (NMDA) receptors15,16. Here we report that NMDA receptor agonists selectively and effectively depress N-type Ca2+ channels which are involved in neurotransmitter release from presynaptic sites. The inhibitory effect is eliminated by the competitive NMDA antagonist D-2-amino-5-phosphonovalerate, does not require Ca2+ entry into the cell, and is probably receptor-mediated. This phenomenon may provide a negative feedback between the liberation of excitatory transmitter and entry of Ca2+ into the cell, and could be important in presynaptic inhibition and in the regulation of synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)418-420
Number of pages3
JournalNature
Volume349
Issue number6308
StatePublished - Jan 31 1991
Externally publishedYes

Fingerprint

N-Type Calcium Channels
N-Methylaspartate
N-Methyl-D-Aspartate Receptors
Synaptic Transmission
Neurotransmitter Agents
Dihydropyridines
2-Amino-5-phosphonovalerate
Neurons
Neuronal Plasticity
Calcium Channels
Ion Channels
Hippocampus

ASJC Scopus subject areas

  • General

Cite this

Chernevskaya, N. I., Obukhov, A., & Krishtal, O. A. (1991). NMDA receptor agonists selectively block N-type calcium channels in hippocampal neurons. Nature, 349(6308), 418-420.

NMDA receptor agonists selectively block N-type calcium channels in hippocampal neurons. / Chernevskaya, Natalya I.; Obukhov, Alexander; Krishtal, Oleg A.

In: Nature, Vol. 349, No. 6308, 31.01.1991, p. 418-420.

Research output: Contribution to journalArticle

Chernevskaya, NI, Obukhov, A & Krishtal, OA 1991, 'NMDA receptor agonists selectively block N-type calcium channels in hippocampal neurons', Nature, vol. 349, no. 6308, pp. 418-420.
Chernevskaya, Natalya I. ; Obukhov, Alexander ; Krishtal, Oleg A. / NMDA receptor agonists selectively block N-type calcium channels in hippocampal neurons. In: Nature. 1991 ; Vol. 349, No. 6308. pp. 418-420.
@article{22cbf8c096a34588af36a2492a5727a3,
title = "NMDA receptor agonists selectively block N-type calcium channels in hippocampal neurons",
abstract = "THE modulation of voltage-dependent calcium channels by various neurotransmitters has been demonstrated in many neurons1-4. Because of the critical role of Ca2+ in transmitter release and, more generally, in transmembrane signalling, this modulation has important functional implications. Hippocampal neurons possess low-threshold (T-type) Ca2+ channels and both L- and N-type high voltage-activated Ca2+ channels.5-7 N-type Ca2+ channels are blocked selectively by ω-conotoxin8,9 and adenosine10,11. These substances both block excitatory synaptic transmission in the hippocampus12-13, whereas dihydropyridines, which selectively block L-type channels14, are ineffective12. Excitatory synaptic transmission in the hippocampus displays a number of plasticity phenomena that are initiated by Ca2+ entry through ionic channels operated by N-methyl-D-aspartate (NMDA) receptors15,16. Here we report that NMDA receptor agonists selectively and effectively depress N-type Ca2+ channels which are involved in neurotransmitter release from presynaptic sites. The inhibitory effect is eliminated by the competitive NMDA antagonist D-2-amino-5-phosphonovalerate, does not require Ca2+ entry into the cell, and is probably receptor-mediated. This phenomenon may provide a negative feedback between the liberation of excitatory transmitter and entry of Ca2+ into the cell, and could be important in presynaptic inhibition and in the regulation of synaptic plasticity.",
author = "Chernevskaya, {Natalya I.} and Alexander Obukhov and Krishtal, {Oleg A.}",
year = "1991",
month = "1",
day = "31",
language = "English (US)",
volume = "349",
pages = "418--420",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6308",

}

TY - JOUR

T1 - NMDA receptor agonists selectively block N-type calcium channels in hippocampal neurons

AU - Chernevskaya, Natalya I.

AU - Obukhov, Alexander

AU - Krishtal, Oleg A.

PY - 1991/1/31

Y1 - 1991/1/31

N2 - THE modulation of voltage-dependent calcium channels by various neurotransmitters has been demonstrated in many neurons1-4. Because of the critical role of Ca2+ in transmitter release and, more generally, in transmembrane signalling, this modulation has important functional implications. Hippocampal neurons possess low-threshold (T-type) Ca2+ channels and both L- and N-type high voltage-activated Ca2+ channels.5-7 N-type Ca2+ channels are blocked selectively by ω-conotoxin8,9 and adenosine10,11. These substances both block excitatory synaptic transmission in the hippocampus12-13, whereas dihydropyridines, which selectively block L-type channels14, are ineffective12. Excitatory synaptic transmission in the hippocampus displays a number of plasticity phenomena that are initiated by Ca2+ entry through ionic channels operated by N-methyl-D-aspartate (NMDA) receptors15,16. Here we report that NMDA receptor agonists selectively and effectively depress N-type Ca2+ channels which are involved in neurotransmitter release from presynaptic sites. The inhibitory effect is eliminated by the competitive NMDA antagonist D-2-amino-5-phosphonovalerate, does not require Ca2+ entry into the cell, and is probably receptor-mediated. This phenomenon may provide a negative feedback between the liberation of excitatory transmitter and entry of Ca2+ into the cell, and could be important in presynaptic inhibition and in the regulation of synaptic plasticity.

AB - THE modulation of voltage-dependent calcium channels by various neurotransmitters has been demonstrated in many neurons1-4. Because of the critical role of Ca2+ in transmitter release and, more generally, in transmembrane signalling, this modulation has important functional implications. Hippocampal neurons possess low-threshold (T-type) Ca2+ channels and both L- and N-type high voltage-activated Ca2+ channels.5-7 N-type Ca2+ channels are blocked selectively by ω-conotoxin8,9 and adenosine10,11. These substances both block excitatory synaptic transmission in the hippocampus12-13, whereas dihydropyridines, which selectively block L-type channels14, are ineffective12. Excitatory synaptic transmission in the hippocampus displays a number of plasticity phenomena that are initiated by Ca2+ entry through ionic channels operated by N-methyl-D-aspartate (NMDA) receptors15,16. Here we report that NMDA receptor agonists selectively and effectively depress N-type Ca2+ channels which are involved in neurotransmitter release from presynaptic sites. The inhibitory effect is eliminated by the competitive NMDA antagonist D-2-amino-5-phosphonovalerate, does not require Ca2+ entry into the cell, and is probably receptor-mediated. This phenomenon may provide a negative feedback between the liberation of excitatory transmitter and entry of Ca2+ into the cell, and could be important in presynaptic inhibition and in the regulation of synaptic plasticity.

UR - http://www.scopus.com/inward/record.url?scp=0025924453&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025924453&partnerID=8YFLogxK

M3 - Article

C2 - 1671527

AN - SCOPUS:0025924453

VL - 349

SP - 418

EP - 420

JO - Nature

JF - Nature

SN - 0028-0836

IS - 6308

ER -