GABAB 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 trapezoid body (MNTB) offer a unique opportunity to explore the modulation of presynaptic channels at a mammalian central synapse. In this study I examined gamma-aminobutyric acid-B (GABA(B))-mediated presynaptic inhibition at the calyx of Held in slices of the rat auditory brain stem. The selective GABA(B) agonist baclofen caused a potent inhibition of synaptic transmission and presynaptic Ca2+ current. The inhibition of presynaptic Ca2+ channels was associated with a slowing of the activation kinetics of the underlying current, and the inhibition was relieved by strong depolarization. The inhibition of both synaptic transmission 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 conductance in the presynaptic terminal. Taken together, these results suggest that GABA(B) receptors inhibit synaptic transmission via G protein-mediated modulation of presynaptic Ca2+ channels at this large central synapse. Furthermore, these findings demonstrate that basic mechanisms of G protein-mediated inhibition of Ca2+ channels, proposed from recordings of neuron cell bodies, are well conserved at nerve endings in the mammalian brain.