MUCOSAL STIMULATION ACTIVATES SUBMUCOSAL SECRETOMOTOR NEURONS VIA LONG DESCENDING MYENTERIC PATHWAYS IN GUINEA PIG ILEUM

DE Reed, S Vanner

GI Diseases Research Unit, Queen's University, Kingston, Ontario

Mucosal stimulation activates intestinal secretion but the properties of enteric reflexes mediating these responses are poorly understood. This study examines whether stimulation of axons in the mucosa activates electrophysiologically identified submucosal secretomotor neurons and if so, which pathways are involved. A full thickness ileal in vitro model was developed which enabled intracellular recording from single submucosal secretomotor neurons from the mucosal stripped aboral segment of the preparation and electrical stimulation of the mucosa in the oral segment. The bipolar stimulating electrode was positioned 6-10 mm from the recording site. Submucosal neurons (n=43) had a mean resting membrane potential of 52.1±1.6 mV. A single electrical stimulus evoked a fast excitatory postsynaptic potential (EPSP) in 24/30 neurons and these elicited action potentials in some cells. To ensure that electrical stimulation activated mucosal axons, the mucosa was severed from the underlying layers and repositioned. In these experiments, fast EPSP's were not elicited in 7/8 neurons. Lesioning studies were conducted to determine if the mucosal activated responses were mediated by the submucosal and/or myenteric plexus. When the myenteric plexus was cut between the stimulating and recording sites, no fast EPSP's were recorded (4/4 neurons). Conversely, fast EPSP's could still be recorded when the submucosal plexus was lesioned. The nicotinic antagonist, hexamethonium, blocked fast EPSP's and long stimulus latencies were observed (mean = 26.9 ± 2.2 ms). Together, these findings are consistent with activation of long polysynaptic pathways through the myenteric plexus. To examine whether 5-HT could effect this pathway, we examined the numbers of fast EPSP's elicited by a stimulus train (10 Hz, 400 ms) before and after application of 5-HT to the mucosal stimulating site. 5-HT increased the amplitude and frequency of fast EPSP's. These studies demonstrate that axons in the mucosa activate long descending secretomotor reflexes. Activation of these reflexes may involve 5-HT and their projections through the myenteric plexus may enable coordination of intestinal motility and secretion.