Neuronal pathways and transmission to the lower esophageal sphincter of the guinea Pig.

Abstract

The lower esophageal sphincter (LES) normally controls the opening and closing of the gastroesophageal junction to resist gastric reflux but allow swallowing. Neuronal pathways controlling the guinea pig LES were investigated anatomically and physiologically in isolated preparations. Intracellular recording from the LES with focal electrical stimulation and retrograde and anterograde neuronal tracing were used. Electrical stimulation on the LES evoked inhibitory junction potentials (IJPs), which were reduced by 60% by 100 micromol/L N-nitro-L-arginine and subsequently blocked by 0.5 micromol/L apamin, unmasking excitatory junction potentials, which were abolished by 1 micromol/L hyoscine. Esophageal or vagal stimulation evoked IJPs, which were blocked by 100 micromol/L hexamethonium. Focal stimulation of the upper stomach evoked IJPs at 5-8 of 20 stimulation sites, which were abolished by cutting between the stimulation site and sphincter. Application of 1,1'-didodecyl-3,3,3', 3'-tetramethyl indocarbocyanine perchlorate (DiI) to the gastric sling muscle anterogradely labeled many motor axons in the sling muscle but few in the LES, confirming that the two muscles are separately innervated. DiI on the esophagus labeled nerve fibers, but not cell bodies, in the upper stomach. The inhibitory motor neurons of the LES receive inputs from the vagus nerve, esophagus, and upper stomach.