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The Journal of Neuroscience, December 1, 1999, 19(23):10305-10317
Identification and Characterization of Glucoresponsive Neurons in
the Enteric Nervous System
Min-tsai
Liu1, 2,
Susumu
Seino3, and
Annette L.
Kirchgessner1, 2
1 Department of Physiology and Pharmacology, State
University of New York Health Science Center at Brooklyn, Brooklyn, New
York 11203, 2 Department of Anatomy and Cell Biology,
Columbia University College of Physicians and Surgeons, New York, New
York 10032, and 3 Department of Molecular Medicine, Chiba
University Graduate School of Medicine, 1-8-1, Inohana, Chuo-ku,
Chiba 260-8670, Japan
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  -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 when
D- mannoheptulose, a hexokinase inhibitor, was present on the reintroduction of glucose. Application of the KATP
channel 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.
Key words:
ATP-sensitive K+ channels; Kir6.2; SUR1; electrophysiology; diazoxide; tolbutamide; leptin; colonic motility
Copyright © 1999 Society for Neuroscience 0270-6474/99/192310305-13$05.00/0
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