Identification and characterization of glucoresponsive neurons in the enteric nervous system

M Liu, S Seino, AL Kirchgessner - Journal of Neuroscience, 1999 - Soc Neuroscience
M Liu, S Seino, AL Kirchgessner
Journal of Neuroscience, 1999Soc Neuroscience
We tested the hypothesis that a subset of enteric neurons is glucoresponsive and expresses
ATP-sensitive K+ (KATP) channels. The immunoreactivities of the inwardly rectifying K+
channel 6.2 (Kir6. 2) and the sulfonylurea receptor (SUR), now renamed SUR1, subunits of
pancreatic β-cell KATP channels, were detected on cholinergic neurons in the guinea pig
ileum, many of which were identified as sensory by their costorage of substance P and/or
calbindin. Glucoresponsive neurons were distinguished in the myenteric plexus because of …
We tested the hypothesis that a subset of enteric neurons is glucoresponsive and expresses ATP-sensitive K+(KATP) channels. The immunoreactivities of the inwardly rectifying K+ channel 6.2 (Kir6.2) and the sulfonylurea receptor (SUR), now renamed SUR1, subunits of pancreatic β-cell KATP channels, were detected on cholinergic neurons in the guinea pig ileum, many of which were identified as sensory by their costorage of substance P and/or calbindin. Glucoresponsive neurons were distinguished in the myenteric plexus because of the hyperpolarization and decrease in membrane input resistance that were observed in response to removal of extracellular glucose. The effects of no-glucose were reversed on the reintroduction of glucose or by the KATP channel inhibitor tolbutamide. No reversal of the hyperpolarization was observed whend- mannoheptulose, a hexokinase inhibitor, was present on the reintroduction of glucose. Application of the KATPchannel opener diazoxide or the ob gene product leptin mimicked the effect of glucose removal in a reversible manner; moreover, hyperpolarizations evoked by either agent were inhibited by tolbutamide. Glucoresponsive neurons displayed leptin receptor immunoreactivity, which was widespread in both enteric plexuses. Superfusion of diazoxide inhibited fast synaptic activity in myenteric neurons, via activation of presynaptic KATP channels. Diazoxide also produced a decrease in colonic motility. These experiments demonstrate for the first time the presence of glucoresponsive neurons in the gut. We propose that the glucose-induced excitation of these neurons be mediated by inhibition of KATP channels. The results support the idea that enteric KATP channels play a role in glucose-evoked reflexes.
Soc Neuroscience