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 patch-clamp technique to study the effect of neuronal nicotinic acetylcholine receptor activation on synaptic transmission. In voltage-clamped neurons, bath application of nicotine (1-30 microM) elicited a concentration-dependent increase in the frequency of the spontaneous synaptic currents. The effect was also observed with application of the nicotinic receptor agonists epibatidine (10 nM) and cytisine (10 microM). Mecamylamine (20 microM) and curare (50 microM), two nicotinic receptor antagonists, both decreased the effect of 3 microM nicotine on the frequency of the spontaneous postsynaptic currents. This effect of 3 microM nicotine was also blocked by 20 microM bicuculline, a competitive antagonist of the GABA(A) receptor; in contrast, it was not affected by 1 mM kynurenic acid, an antagonist of the ionotropic glutamate receptor. In the presence of 1 microM tetrodotoxin, 3 microM nicotine was unable to affect the synaptic activity. Our findings suggest the existence of nicotinic receptors on GABAergic axons projecting to the vagal motoneurons. Because the effect is completely abolished by 1 microM tetrodotoxin, the nicotinic 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 of nicotinic receptor activation on spontaneous GABA release in the dorsal motor nucleus of the vagus may have an important role in the regulation of gastrointestinal motility.
Bertolino
M
M
Department of Pharmacology, Georgetown University, School of Medicine, Washington, D.C. 20007, U.S.A.
Kellar
K J
KJ
Vicini
S
S
Gillis
R A
RA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001933:Brain Stem / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011978:Receptors, Nicotinic; D005680:gamma-Aminobutyric Acid; D009538:Nicotine; D000109:Acetylcholine