title: Electrophysiological identification of glucose-sensing neurons in rat nodose ganglia.
abstract: The vagal afferent system is strategically positioned to mediate rapid changes in motility and satiety in response to systemic glucose levels. In the present study we aimed to identify glucose-excited and glucose-inhibited neurons in nodose ganglia and characterize their glucose-sensing properties. Whole-cell patch-clamp recordings in vagal afferent neurons isolated from rat nodose ganglia demonstrated that 31/118 (26%) neurons were depolarized after increasing extracellular glucose from 5 to 15 mm; 19/118 (16%) were hyperpolarized, and 68/118 were non-responsive. A higher incidence of excitatory response to glucose occurred in gastric- than in portal vein-projecting neurons, the latter having a higher incidence of inhibitory response. In glucose-excited neurons, elevated glucose evoked membrane depolarization (11 mV) and an increase in membrane input resistance (361 to 437 M). Current reversed at 99 mV. In glucose-inhibited neurons, membrane hyperpolarization (13 mV) was associated with decreased membrane input resistance (383 to 293 M). Current reversed at 97 mV. Superfusion of tolbutamide, a K(ATP) channel sulfonylurea receptor blocker, elicited identical glucose-excitatory but not glucose-inhibitory responses. Kir6.2 shRNA transfection abolished glucose-excited but not glucose-inhibited responses. Phosphatidylinositol bisphosphate (PIP(2)) depletion using wortmannin increased the fraction of glucose-excited neurons from 26% to 80%. These results show that rat nodose ganglia have glucose-excited and glucose-inhibited neurons, differentially distributed among gastric- and portal vein-projecting nodose neurons. In glucose-excited neurons, glucose metabolism leads to K(ATP) channel closure, triggering membrane depolarization, whereas in glucose-inhibited neurons, the inhibitory effect of elevated glucose is mediated by an ATP-independent K(+) channel. The results also show that PIP(2) can determine the excitability of glucose-excited neurons.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA.
authors.forename: Gintautas
authors.initials: G
authors.lastname: Grabauskas
authors.forename: Il
authors.initials: I
authors.lastname: Song
authors.forename: Shiyi
authors.initials: S
authors.lastname: Zhou
authors.forename: Chung
authors.initials: C
authors.lastname: Owyang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D005260:Female; D005947:Glucose / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000502:physiology; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D064233:Sulfonylurea Receptors; D014044:Tolbutamide / Q000494:pharmacology; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D000077191:Wortmannin; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D000730:Androstadienes; D005947:Glucose; D019269:Phosphatidylinositol 4,5-Diphosphate; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D014044:Tolbutamide; D000077191:Wortmannin; D000099161:Kcnj11 Channel