The Journal of Neurophysiology Vol. 80 No. 3 September 1998, pp. 1571-1576
Copyright ©1998 The American Physiological Society

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GABA_B Receptor-Mediated Modulation of Presynaptic Currents and Excitatory Transmission at a Fast Central Synapse

Jeffry S. Isaacson

Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195

Isaacson, Jeffry S. GABA_B receptor-mediated modulation of presynaptic currents and excitatory transmission at a fast central synapse. J. Neurophysiol. 80: 1571-1576, 1998. 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 -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.

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