Nonuniform distribution of Ca²⁺ channel subtypes on presynaptic terminals of excitatory synapses in hippocampal cultures

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.