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Volume 17, Number 8, Issue of April 15, 1997 pp. 2738-2745
Copyright ©1997 Society for Neuroscience

Nonuniform Distribution of Ca²⁺ Channel Subtypes on Presynaptic Terminals of Excitatory Synapses in Hippocampal Cultures

Received Oct. 15, 1996; revised Jan. 6, 1997; accepted Feb. 7, 1997.

Christopher A. Reid, John D. Clements, and John M. Bekkers

Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia

Several subtypes of Ca²⁺ channel support the release of glutamate at excitatory synapses. We investigated the pattern of colocalization of these subtypes on presynaptic terminals in hippocampal cultures. N-type (conotoxin GVIA-sensitive) or P/Q-type (agatoxin IVA-sensitive) Ca²⁺ channels were blocked selectively, and the reduction in transmitter release probability (P_r) was measured with MK-801. The antagonists completely blocked release at some terminals, reduced P_r at others, and failed to affect the remainder. In contrast, nonselective reduction of presynaptic Ca²⁺ influx by adding Cd²⁺ or lowering external Ca²⁺ reduced P_r uniformly at all terminals. We conclude from these results that the mixture of N-type and P/Q-type channels varies markedly between terminals on the same afferent. The distribution of Ca²⁺ channel subtypes was the same for high and low P_r terminals. Given that Ca²⁺ channel subtypes are affected differentially by neuromodulators, these findings lead to the possibility of terminal-specific modulation of synaptic function.

Key words: calcium channel; MK-801; NMDA; quantal analysis; release probability; synaptic transmission

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