Adiponectin modulates excitability of rat paraventricular nucleus neurons by differential modulation of potassium currents.
The adipocyte-derived hormone adiponectin acts at two seven-transmembrane domain receptors, adiponectin receptor 1 and adiponectin receptor 2, present in the paraventricular nucleus of the hypothalamus to regulate neuronal excitability and endocrine function. Adiponectin depolarizes rat parvocellular preautonomic neurons that secrete either thyrotropin releasing hormone or oxytocin and parvocellular neuroendocrine corticotropin releasing hormone neurons, leading to an increase in plasma adrenocorticotropin hormone concentrations while also hyperpolarizing a subgroup of neurons. In the present study, we investigate the ionic mechanisms responsible for these changes in excitability in parvocellular paraventricular nucleus neurons. Patch clamp recordings of currents elicited from slow voltage ramps and voltage steps indicate that adiponectin inhibits noninactivating delayed rectifier potassium current (I(K)) in a majority of neurons. This inhibition produced a broadening of the action potential in cells that depolarized in the presence of adiponectin. The depolarizing effects of adiponectin were abolished in cells pretreated with tetraethyl ammonium (0/15 cells depolarize). Slow voltage ramps performed during adiponectin-induced hyperpolarization indicate the activation of voltage-independent potassium current. These hyperpolarizing responses were abolished in the presence of glibenclamide [an ATP-sensitive potassium (K(ATP)) channel blocker] (0/12 cells hyperpolarize). The results presented in this study suggest that adiponectin controls neuronal excitability through the modulation of different potassium conductances, effects which contribute to changes in excitability and action potential profiles responsible for peptidergic release into the circulation.
Hoyda
Ted D
TD
Department of Physiology, Queen's University, 4th Floor Botterell Hall, Kingston, Ontario, Canada K7L 3N6.
Ferguson
Alastair V
AV
D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology*; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D019789:Tetraethylammonium / Q000494:pharmacology
D052242:Adiponectin; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019789:Tetraethylammonium; D011188:Potassium; D005905:Glyburide