Js. Isaacson, GABA(B) RECEPTOR-MEDIATED MODULATION OF PRESYNAPTIC CURRENTS AND EXCITATORY TRANSMISSION AT A FAST CENTRAL SYNAPSE, Journal of neurophysiology, 80(3), 1998, pp. 1571-1576
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.