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Neural Integration of Peripheral Signals Implicated in the Control of Energy Homeostasis and Metabolism

Ghrelin modulates electrical activity of area postrema neurons

Department of Physiology, Queen's University, Kingston, Ontario, Canada

Submitted 30 June 2008 ; accepted in final form 27 December 2008

Ghrelin, a peptide hormone secreted from the stomach, is known to have a potent appetite-stimulating activity. Recently, it has been shown that area postrema (AP), a caudal brain stem center that lacks a blood-brain barrier, is a key site of activity for ghrelin in stimulating appetite and regulating pancreatic protein secretion. In this study, we have examined the ability of ghrelin to regulate the electrical activity of area postrema neurons using patch-clamp electrophysiology. Using current-clamp configuration, we found that at a concentration of 10 nM, ghrelin caused inhibition in 19% of neurons tested, while a further 19% were excited by similar application of ghrelin. The remaining 62% of AP neurons were insensitive to ghrelin. These effects were concentration dependent, with an apparent EC₅₀ of 1.9 nM. Voltage-clamp recordings revealed that ghrelin caused a potentiation of voltage-gated K⁺ currents in neurons that exhibited a hyperpolarization and a potentiation of a depolarizing nonspecific cation current (NSCC) in those neurons that exhibited a depolarization of membrane potential. These are the first data showing that ghrelin exerts a direct effect on electrical activity of AP neurons and supports the notion that ghrelin can act via the AP to regulate energy homeostasis.

patch clamp; action potential; sensory circumventricular organ; energy homeostasis