Calcium channel types with distinct presynaptic localization couple differentially to transmitter release in single calyx-type synapses

We studied how Ca2+ influx through different subtypes of Ca2+ channels coup les to release at a calyx-type terminal in the rat medial nucleus of the tr apezoid body by simultaneously measuring the presynaptic Ca2+ influx evoked by a single action potential and the EPSC. Application of subtype-specific toxins showed that Ca2+ channels of the P/Q-, N-, and R-type controlled gl utamate release at a single terminal. The Ca2+ influx through the P/Q-type channels triggered release more effectively than Ca2+ influx through N- or R-type channels. We investigated mechanisms that contributed to these diffe rences in effectiveness. Electrophysiological experiments suggested that in dividual release sites were controlled by all three subtypes of Ca2+ channe ls. Immunocytochemical staining indicated, however, that a substantial frac tion of N- and R-type channels was located distant from release sites. Alth ough these distant channels contributed to the Ca2+ influx into the termina l, they may not contribute to release. Taken together, the results suggest that the Ca2+ influx into the calyx via N- and R-type channels triggers rel ease less effectively than that via P/Q-type because a substantial fraction of the N- and R-type channels in the calyx is localized distant from relea se sites.