NICOTINIC RECEPTOR MEDIATES SPONTANEOUS GABA RELEASE IN THE RAT DORSAL MOTOR NUCLEUS OF THE VAGUS

Spontaneous postsynaptic currents were investigated in neurons of the caudal portion of the dorsal motor nucleus of the vagus using the patc h-clamp technique to study the effect of neuronal nicotinic acetylchol ine receptor activation on synaptic transmission. In voltage-clamped n eurons, bath application of nicotine (1-30 mu M) elicited a concentrat ion-dependent increase in the frequency of the spontaneous synaptic cu rrents. The effect was also observed with application of the nicotinic receptor agonists epibatidine (10 nM) and cytisine (10 mu M). Mecamyl amine (20 mu M) and curare (50 mu M), two nicotinic receptor antagonis ts, both decreased the effect of 3 mu M nicotine on the frequency of t he spontaneous postsynaptic currents. This effect of 3 mu M nicotine w as also blocked by 20 mu M bicuculline, a competitive antagonist of th e GABA(A) receptor; in contrast, it was not affected by 1 mM kynurenic acid, an antagonist of the ionotropic glutamate receptor. In the pres ence of 1 mu M tetrodotoxin, 3 mu M nicotine was unable to affect the synaptic activity. Our findings suggest the existence of nicotinic rec eptors on GABAergic axons projecting to the vagal motoneurons. Because the effect is completely abolished by 1 mu M tetrodotoxin, the nicoti nic receptors are not localized on the presynaptic nerve terminal and their action on the GABA release requires the propagation of an action potential from their location to the synaptic terminal. This effect o f nicotinic receptor activation on spontaneous GABA release in the dor sal motor nucleus of the vagus may have an important role in the regul ation of gastrointestinal motility. (C) 1997 IBRO. Published by Elsevi er Science Ltd.