Nicotinic cholinoceptor-mediated excitation in ambigual motoneurons of the rat

Abstract

The purpose of this study was to determine if ambigual oesophageal motoneurons of the rat possess functional nicotinic cholinoceptors. In urethane anaesthetized rats, acetylcholine (20–50 pmol) delivered micropneumophoretically from multibarrelled pipettes to the compact formation of the nucleus ambiguus produced either synchronous or propulsive oesophageal contractions which were fully and reversibly blocked by dihydro-β-erythroidine (8–10 pmol) but were resistant to d-tubocurarine and hexamethonium (10–20 pmol). 1,1-Dimethyl-4-phenyl-piperazinium but not muscarine (8 pmol) exerted an analogous agonist action. Ejection of glutamate at the same sites produced similar oesophageal responses which were, however, resistant to dihydro-β-erythroidine. Acetylcholine applied 5–15 s prior to glutamate transiently facilitated the glutamate-evoked response. The facilitatory effect of acetylcholine was replicated by 1,1-dimethyl-4-phenyl-piperazinium but not muscarine and inhibited by dihydro-β-ery-throidine. Physostigmine, applied either intra-ambigually (10–20 pmol) or by intravenous injection (0.15–0.3 μmol/kg), enhanced both acetylcholine and glutamate-evoked responses. In brainstem transverse slices, application of acetylcholine and glutamate to quiescent ambigual neurons of the compact formation resulted in a rapid membrane depolarization associated with an increased membrane conductance and spiking. Under voltage clamp, both acetylcholine and glutamate elicited a net inward current. The depolarizing response of these neurons to acetylcholine was blocked by dihydro-β-erythroidine (0.5–2 pmol), hexamethonium (0.2 mM) and d-tubocurarine (10 μM) and persisted in the presence of tetrodotoxin (10 −6 M) or Mn 2+ (5 mM) in the bathing medium. It is concluded that functional postsynaptic nicotinic cholinoceptors are present on ambigual oesophageal motoneurons, and that nicotinic receptor-mediated transmission may play a role in oesophageal peristalsis at the motoneuronal level.