NMDA RECEPTOR AGONISTS SELECTIVELY BLOCK N-TYPE CALCIUM CHANNELS IN HIPPOCAMPAL-NEURONS

THE modulation of voltage-dependent calcium channels by various neurotransmitters had been demonstrated in many neurons 1-4,. Because of the critical role of Ca2+ in transmitter release and, more generally, in transmembrane signalling, this modulation has important functional implications. Hippocampal neurons posses 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 omega-conotoxin 8, 9 and adenosine 10, 11. These substances both block excitatory synaptic transmission in the hippocampus 12-13, whereas dihydropyridines, which selectively block L-type channels 14, are ineffective 12. 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 15, 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.