R-type Ca2+ currents evoke transmitter release at a rat central synapse

Voltage-dependent [Ca.sup.2+] currents evoke synaptic transmitter release. Of six types of [Ca.sup.2+] channels, L-, N-, P-, Q-, R-, and T-type, only N- and P/Q-type channels have been pharmacologically identified to mediate action-potential-evoked transmitter release in the mammalian central nervous system. We tested whether [Ca.sup.2+] channels other than N- and P/Q-type control transmitter release in a calyx-type synapse of the rat medial nucleus of the trapezoid body. Simultaneous recordings of presynaptic [Ca.sup.2+] influx and the excitatory postsynaptic current evoked by a single action potential were made at single synapses. The R-type channel, a high-voltage-activated [Ca.sup.2+] channel resistant to L-, N-, and P/Q-type channel blockers, contributed 26% of the total [Ca.sup.2+] influx during a presynaptic action potential. This [Ca.sup.2+] current evoked transmitter release sufficiently large to initiate an action potential in the postsynaptic neuron. The R-type current controlled release with a lower efficacy than other types of [Ca.sup.2+] currents. Activation of metabotropic glutamate receptors and [Gamma]-aminobutyric acid type B receptors inhibited the R-type current. Because a significant fraction of presynaptic [Ca.sup.2+] channels remains unidentified in many other central synapses, the R-type current also could contribute to evoked transmitter release in these synapses.