Background & Aims: The lower esophageal sphincter (LES) normally contr
ols the opening and closing of the gastroesophageal junction to resist
gastric reflux but allow swallowing. Neuronal pathways controlling th
e guinea pig LES were investigated anatomically and physiologically in
isolated preparations. Methods: Intracellular recording from the LES
with focal electrical stimulation and retrograde and anterograde neuro
nal tracing were used. Results: Electrical stimulation on the LES evok
ed inhibitory junction potentials (IJPs), which were reduced by 60% by
100 mu mol/L N-nitro-L-arginine and subsequently blocked by 0.5 mu mo
l/L apamin, unmasking excitatory junction potentials, which were aboli
shed by 1 mu mol/L hyoscine, Esophageal or vagal stimulation evoked IJ
Ps, which were blocked by 100 mu mol/L hexamethonium. Focal stimulatio
n of the upper stomach evoked IJPs at 5-8 of 20 stimulation sites, whi
ch were abolished by cutting between the stimulation site and sphincte
r, Application of 1,1'-didodecyl-3,3,3',3'-tetramethyl indocarbocyanin
e perchlorate (Dil) to the gastric sling: muscle anterogradely labeled
many motor axons in the sling muscle but few in the LES, confirming t
hat the two muscles are separately innervated. Dir on the esophagus la
beled nerve fibers, but not cell bodies, in the upper stomach, Conclus
ions: The inhibitory motor neurons of the LES receive inputs from the
vagus nerve, esophagus, and upper stomach.