GABA(B) RECEPTOR-MEDIATED MODULATION OF PRESYNAPTIC CURRENTS AND EXCITATORY TRANSMISSION AT A FAST CENTRAL SYNAPSE

Large nerve terminals (calyces of Held) in the medial nucleus of the t rapezoid body (MNTB) offer a unique opportunity to explore the modulat ion of presynaptic channels at a mammalian central synapse. In this st udy I examined gamma-aminobutyric acid-B (GABA(B))-mediated presynapti c inhibition at the calyx of Held in slices of the rat auditory brain stem. The selective GABA(B) agonist baclofen caused a potent inhibitio n of synaptic transmission and presynaptic Ca2+ current. The inhibitio n of presynaptic Ca2+ channels was associated with a slowing of the ac tivation kinetics of the underlying current, and the inhibition was re lieved by strong depolarization. The inhibition of both synaptic trans mission and presynaptic Ca2+ current was abolished by N-ethylmaleimide , a sulfhydryl alkylating agent that uncouples the G(o)/G(i) class of G proteins from receptors. Baclofen does not activate a potassium cond uctance in the presynaptic terminal. Taken together, these results sug gest that GABA(B) receptors inhibit synaptic transmission via G protei n-mediated modulation of presynaptic Ca2+ channels at this large centr al synapse. Furthermore, these findings demonstrate that basic mechani sms of G protein-mediated inhibition of Ca2+ channels, proposed from r ecordings of neuron cell bodies, are well conserved at nerve endings i n the mammalian brain.