Calcium Channel Types with Distinct Presynaptic Localization Couple Differentially to Transmitter Release in Single Calyx-Type Synapses

Abstract

We studied how Ca ²⁺ influx through different subtypes of Ca ²⁺ channels couples to release at a calyx-type terminal in the rat medial nucleus of the trapezoid body by simultaneously measuring the presynaptic Ca ²⁺ influx evoked by a single action potential and the EPSC. Application of subtype-specific toxins showed that Ca ²⁺ channels of the P/Q-, N-, and R-type controlled glutamate release at a single terminal. The Ca ²⁺influx through the P/Q-type channels triggered release more effectively than Ca ²⁺ influx through N- or R-type channels. We investigated mechanisms that contributed to these differences in effectiveness. Electrophysiological experiments suggested that individual release sites were controlled by all three subtypes of Ca ²⁺ channels. Immunocytochemical staining indicated, however, that a substantial fraction of N- and R-type channels was located distant from release sites. Although these distant channels contributed to the Ca ²⁺ influx into the terminal, they may not contribute to release. Taken together, the results suggest that the Ca ²⁺ influx into the calyx via N- and R-type channels triggers release 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 release sites.