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 (GABAB)-mediated presynaptic inhibition at the calyx of Held in slices of the rat auditory brain stem. The selective GABAB 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)/Gi class of G proteins from receptors. Baclofen does not activate a potassium conductance in the presynaptic terminal. Taken together, these results suggest that GABAB 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.
Isaacson
J S
JS
Department of Physiology and Biophysics, University of Washington, Seattle 98195, USA.
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001306:Auditory Pathways / Q000737:chemistry / Q000502:physiology; D001418:Baclofen / Q000494:pharmacology; D001933:Brain Stem / Q000737:chemistry / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000737:chemistry / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D011810:Quinoxalines; D018080:Receptors, GABA-B; C056723:FG 9041; D015763:2-Amino-5-phosphonovalerate; D001418:Baclofen; D005033:Ethylmaleimide