Submitted on July 1, 2008
Revised on November 18, 2008
Accepted on December 27, 2008
Ghrelin modulates electrical activity of area postrema neurons
Mark Fry1 and Alastair V. Ferguson2*
1 University of Manitoba
2 Queen's University
* To whom correspondence should be addressed. E-mail: avf{at}queensu.ca.
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 brainstem centre 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 physiological 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 non-specific cation conductance (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.
