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Department of Physiology and Biophysics, Mayo Clinic, Rochester, MN 55905.

1. GABA receptor-modulating drugs and intracellular recording techniques were used to determine the functional significance of peripheral afferent GABA-containing nerves projecting from the distal colon to sympathetic neurones in the inferior mesenteric ganglion of the guinea-pig. 2. GABAA receptor-modulating drugs added selectively to the inferior mesenteric ganglion side of a two-compartment bath had pronounced effects on on-going colonic afferent cholinergic synaptic input. Bicuculline (20 microM) decreased the amplitude and frequency of fast excitatory postsynaptic potentials (EPSPs) by 40% whereas diazepam (5 microM) increased cholinergic input by 43%. Neither drug had any effect on the resting membrane potential or membrane input resistance of ganglion cells. 3. Bicuculline (20 microM) significantly reduced, whereas diazepam (5 microM) significantly enhanced, distension-induced increases in nicotinic fast EPSPs and action potentials. 4. Slow EPSPs evoked by colonic distension were not affected by bicuculline or diazepam. 5. Manual voltage clamp of the postsynaptic depolarizing response to exogenous GABA revealed 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 GABAA receptors to facilitate release of acetylcholine from colonic mechanosensory nerves.

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