The electrophysiological effects of endogenous GABA in the guinea‐pig inferior mesenteric ganglion.

Abstract

SUMMARY1. 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 1uM) decreased the amplitude and frequency of fast excitatory postsynaptic potentials (EPSPs) by 40% whereas diazepam (5 ,M) 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 /2M) significantly reduced, whereas diazepam (5 /tM) 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.

Identification and mechanosensitivity of viscerofugal neurons

“…Viscerofugal neurons typically had low thresholds to distension (showing increased firing at loads of 1 g) but also showed only small increases in firing frequency. This is also consistent with previous reports based on viscerofugal synaptic inputs to prevertebral ganglia (Anthony and Kreulen, 1990;Bywater, 1993;Parkman et al, 1993;Stapelfeldt et al, 1993;Ermilov et al, 2004b).…”

Enteric GABA‐containing nerves projecting to the guinea‐pig inferior mesenteric ganglion modulate acetylcholine release.

“…The effect of these GABAA receptor-modulating drugs is consistent with the notion that endogenous GABA was released from colonic afferent nerves and that it facilitated peripheral cholinergic input. Previous electrophysiological experiments in which intracellular recordings were made from sympathetic neurones in the inferior mesenteric ganglion suggest that endogenously released GABA acts only to modulate nicotinic cholinergic transmission because bicuculline decreases and diazepam increases the amplitude and frequency of nicotinic EPSPs without affecting the amplitude or duration of slow EPSPs or changing the resting membrane potential (Stapelfeldt et al 1993). GABA receptors present in other peripheral ganglia and in the central nervous system modulate cholinergic transmission.…”

“…Using electrophysiological techniques, two effects of GABA have been observed. Exogenous GABA depolarizes sympathetic neurones by acting on postsynaptic GABAA receptors (Hills et al 1988; Stapelfeldt, Parkman & Szurszewski, 1993). Also, endogenously released GABA facilitates fast nicotinic synaptic input by acting on GABAA receptors located presynaptically on colonic mechanosensory afferent nerves (Stapelfeldt et al 1993).…”

“…In these previous experiments, exogenous administration of GABA evoked a depolarization of the membrane potential sufficient to block postsynaptic transmission. Since a postsynaptic depolarization was not observed when GABA was released from endogenous stores (Stapelfeldt et al 1993), it seems reasonable to suggest that under in vivo conditions, the presynaptic effect of GABA may be physiologically more relevant. The functional advantage of postsynaptic GABAB receptors may be a self-protecting mechanism limiting transmission during high-intensity activation of colonic GABA-afferent nerves.…”

Numerical Simulation of Motility Patterns of the Small Bowel. II. Comparative Pharmacological Validation of a Mathematical Model

“…Thus, benzodiazepines potentiate a GABA -mediated ACh release on the soma of AH neurons in a dose-dependent manner. However, at low concentrations, they do not a!ect the contractile activity of smooth muscle (Bertrand & Galligan, 1992;Stapelfeldt et al, 1993). At high concentrations, benzodiazepines abolish GABA -mediated ACh release and severely depress intestinal motility through the activation of GABA receptors on motor neurons.…”