title: Ghrelin reduces voltage-gated potassium currents in GH3 cells via cyclic GMP pathways.
abstract: Ghrelin is an endogenous growth hormone secretagogue (GHS) causing release of GH from pituitary somatotropes through the GHS receptor. Secretion of GH is linked directly to intracellular free Ca(2+) concentration ([Ca(2+)]i), which is determined by Ca(2+) influx and release from intracellular Ca(2+) storage sites. Ca(2+) influx is via voltage-gated Ca(2+) channels, which are activated by cell depolarization. Membrane potential is mainly determined by transmembrane K(+) channels. The present study investigates the in vitroeffect 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 Co(2+) (1 mM, Ca(2+) channel blocker) and tetrodotoxin (1 microM, 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 (IA) represented a significant proportion of total K(+) currents in some cells, whereas delayed rectifier K(+) current (IK) existed in all cells. The application of ghrelin (10 nM) reversibly and significantly decreased the amplitude of both IA and IK currents to 48% and 64% of control, respectively. Application of apamin (1 microM, SK channel blocker) or charybdotoxin (1 microM, 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 ghrelin-induced 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.
authors.affiliation: Department of Physiology, Fourth Military Medical University, Shannxi, China.
authors.forename: Xue Feng
authors.initials: XF
authors.lastname: Han
authors.forename: Yun Long
authors.initials: YL
authors.lastname: Zhu
authors.forename: Maria
authors.initials: M
authors.lastname: Hernandez
authors.forename: Damien J
authors.initials: DJ
authors.lastname: Keating
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D045744:Cell Line, Tumor; D018999:Charybdotoxin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology; D054439:Ghrelin; D013006:Growth Hormone / Q000378:metabolism; D036361:Peptide Hormones / Q000502:physiology*; D010902:Pituitary Gland; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D054440:Receptors, Ghrelin; D015398:Signal Transduction / Q000502:physiology
chemical_list: D054439:Ghrelin; D036361:Peptide Hormones; D024642:Potassium Channels, Voltage-Gated; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D018999:Charybdotoxin; D001030:Apamin; D013006:Growth Hormone; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C; D006152:Cyclic GMP