THE ELECTROPHYSIOLOGICAL EFFECTS OF ENDOGENOUS GABA IN THE GUINEA-PIGINFERIOR MESENTERIC GANGLION

1. GABA receptor-modulating drugs and intracellular recording techniqu es were used to determine the functional significance of peripheral af ferent GABA-containing nerves projecting from the distal colon to symp athetic neurones in the inferior mesenteric ganglion of the guinea-pig . 2. GABA(A) receptor-modulating drugs added selectively to the inferi or mesenteric ganglion side of a two-compartment bath had pronounced e ffects on on-going colonic afferent cholinergic synaptic input. Bicucu lline (20 muM) decreased the amplitude and frequency of fast excitator y postsynaptic potentials (EPSPs) by 40 % whereas diazepam (5 muM) inc reased cholinergic input by 43 %. Neither drug had any effect on the r esting membrane potential or membrane input resistance of ganglion cel ls. 3. Bicuculline (20 muM) significantly reduced, whereas diazepam (5 muM) significantly enhanced, distension-induced increases in nicotini c fast EPSPs and action potentials. 4. Slow EPSPs evoked by colonic di stension were not affected by bicuculline or diazepam. 5. Manual volta ge clamp of the postsynaptic depolarizing response to exogenous GABA r evealed GABA-induced presynaptic facilitation of colonic afferent but not central preganglionic efferent cholinergic synaptic input. 6. The data suggest that endogenously released GABA participates in on-going colo-colonic reflex activity by acting on presynaptic GABA(A) receptor s to facilitate release of acetylcholine from colonic mechanosensory n erves.