NMDA receptor agonists selectively block N-type calcium channels in hippocampal neurons.
The modulation of voltage-dependent calcium channels by various neurotransmitters has been demonstrated in many neurons. 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. N-type Ca2+ channels are blocked selectively by omega-conotoxin and adenosine. These substances both block excitatory synaptic transmission in the hippocampus, whereas dihydropyridines, which selectively block L-type channels, are ineffective. 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) receptors. 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.
Chernevskaya
N I
NI
Bogomoletz Institute of Physiology, Kiev, USSR.
Obukhov
A G
AG
Krishtal
O A
OA
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology; D001224:Aspartic Acid / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects*; D005971:Glutamates / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007736:Kynurenic Acid / Q000494:pharmacology; D008978:Mollusk Venoms / Q000494:pharmacology; D016202:N-Methylaspartate / Q000502:physiology*; D009473:Neuronal Plasticity; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D009435:Synaptic Transmission
D015220:Calcium Channels; D005971:Glutamates; D008978:Mollusk Venoms; D016194:Receptors, N-Methyl-D-Aspartate; D001224:Aspartic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D007736:Kynurenic Acid; D000241:Adenosine; D002118:Calcium