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

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

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

THEmodulation 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.5-7N-type Ca2+ channels are blocked selectively by ω-conotoxin 8,9 and adenosine 10,11. 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 neurotransmit-ter 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
DOIs
StatePublished - Jan 1 1991

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

ASJC Scopus subject areas

  • General

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

In: Nature, Vol. 349, No. 6308, 01.01.1991, p. 418-420.

Research output: Contribution to journalArticle

Chernevskaya, Natalya I. ; Obukhov, Alexander G. ; 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.
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