Ghrelin reduces voltage-gated potassium currents in GH3 cells via cyclic GMP pathways

Feng Han, Xue, Long Zhu, Yun, Hernandez, Maria, Keating, Damien J. and Chen Chen (2005) Ghrelin reduces voltage-gated potassium currents in GH3 cells via cyclic GMP pathways. Endocrine, 28 2: 217-224. doi:10.1385/ENDO:28:2:217


Author Feng Han, Xue
Long Zhu, Yun
Hernandez, Maria
Keating, Damien J.
Chen Chen
Title Ghrelin reduces voltage-gated potassium currents in GH3 cells via cyclic GMP pathways
Journal name Endocrine   Check publisher's open access policy
ISSN 0969-711X
1559-0100
1355-008X
Publication date 2005-11
Year available 2005
Sub-type Article (original research)
DOI 10.1385/ENDO:28:2:217
Volume 28
Issue 2
Start page 217
End page 224
Total pages 8
Editor P. M. Conn
Place of publication Totowa, N.J., U.S.A.
Publisher Humana Press Inc.
Language eng
Subject 110306 Endocrinology
110201 Cardiology (incl. Cardiovascular Diseases)
111201 Cancer Cell Biology
Abstract Ghrelin is an endogeneous growth hormone secretagogue (GHS) causing release of GH from pituitary somatotropes through the GHS receptor. Secretion of GH is linked directly to intracellular free Ca2+ concentration ([Ca2+]i), which is determined by Ca2+ influx and release from intracellular Ca2+ storage sites. Ca2+ influx is via voltage-gated Ca2+ channels, which are activated by cell depolarization. Membrane potential is mainly determined by transmembrane K+ channels. The present study investigates the in vitro effect of ghrelin on membrane voltage-gated K+ channels in the GH3 rat somatotrope cell line. Nystatin-perforated patch clamp recording was used to record K+ currents under voltage-clamp conditions. In the presence of Co2+ (1 mM, Ca2+ channel blocker) and tetrodotoxin (1 µM, Na+ channel blocker) in the bath solution, two types of voltage-gated K+ currents were characterized on the basis of their biophysical kinetics and pharmacological properties. We observed that transient K+ current (I A) represented a significant proportion of total K+ currents in some cells, whereas delayed rectifier K+ current (I K) existed in all cells. The application of ghrelin (10 nM) reversibly and significantly decreased the amplitude of both I A and I K currents to 48% and 64% of control, respectively. Application of apamin (1 µM, SK channel blocker) or charybdotoxin (1 µM, BK channel blocker) did not alter the K+ current or the response to ghrelin. The ghrelin-induced reduction in K+ currents was not affected by PKC and PKA inhibitors. KT5823, a specific PKG inhibitor, totally abolished the K+ current response to ghrelin. These results suggest that ghrelininduced reduction of voltage-gated K+ currents in GH3 cells is mediated through a PKG-dependent pathway. A decrease in voltage-gated K+ currents may increase the frequency, duration, and amplitude of action potentials and contribute to GH secretion from somatotropes.
Keyword Ghrelin
voltage-gated K+ channels
Endocrine glands
Endocrine Diseases
Endocrinology
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
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Created: Tue, 13 Jan 2009, 11:11:46 EST by Ms Karen Naughton on behalf of Institute for Molecular Bioscience