title: Glucose-responsive neurons in the subfornical organ of the rat--a novel site for direct CNS monitoring of circulating glucose.
abstract: Glucose-sensitive neurons have been identified in a number of CNS regions including metabolic control centers of the hypothalamus. The location of these regions behind the blood-brain barrier restricts them to sensing central, but not circulating glucose concentrations. In this study, we have used patch-clamp electrophysiology to examine whether neurons in a specialized region lacking the blood-brain barrier, the subfornical organ (SFO), are also glucose sensitive. In dissociated SFO neurons, altering the bath concentration of glucose (1 mM, 5 mM, 10 mM) influenced the excitability of 49% of neurons tested (n=67). Glucose-inhibited (GI) neurons depolarized in response to decreased glucose (n=10; mean, 4.6±1.0 mV) or hyperpolarized in response to increased glucose (n=8; mean,-4.4±0.8 mV). In contrast, glucose-excited (GE) neurons depolarized in response to increased glucose (n=9; mean, 6.4±0.4 mV) or hyperpolarized in response to decreased glucose (n=6; mean,-4.8±0.6 mV). Using voltage-clamp recordings, we also identified GI (outward current to increased glucose) and GE (inward current to increased glucose) SFO neurons. The mean glucose-induced inward current had a reversal potential of -24±12 mV (n=5), while GE responses were maintained during sodium-dependent glucose transporter inhibition, supporting the conclusion that GE properties result from the activation of a nonselective cation conductance (NSCC). The glucose-induced outward current had a mean reversal potential of -78±1.2 mV (n=5), while GI responses were not observed in the presence of glibenclamide, suggesting that these properties result from the modulation of K(ATP) channels. These data demonstrate that SFO neurons are glucose responsive, further emphasizing the potential roles of this circumventricular organ as an important sensor and integrator of circulating signals of energy status.
authors: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada. avf@queensu.ca
authors: N
authors: N
authors: Medeiros
authors: L
authors: L
authors: Dai
authors: A V
authors: AV
authors: Ferguson
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D055592:Biophysical Phenomena / Q000187:drug effects; D001703:Biophysics; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013356:Subfornical Organ / Q000166:cytology*
chemical_list: D007004:Hypoglycemic Agents; D005947:Glucose; D005905:Glyburide