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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 296/5/E1148    most recent 90954.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dominguez, B. Articles by Monjaraz, E. Search for Related Content PubMed PubMed Citation Articles by Dominguez, B. Articles by Monjaraz, E.

Upregulation of voltage-gated Na⁺ channels by long-term activation of the ghrelin-growth hormone secretagogue receptor in clonal GC somatotropes

¹Laboratory of Neuroendocrinology, Institute of Physiology, Autonomous University of Puebla, Puebla, Mexico; ²Laboratory of Physiology, School of Veterinary Medicine and Zootechny, University of Veracruz, Veracruz; and ³Department of Cell Biology, Center for Research and Advanced Studies of The National Polytechnic Institute, Mexico City, Mexico

Submitted 28 November 2008 ; accepted in final form 11 February 2009

A central question in adenohypophyseal cell physiology concerns the role of transmembrane ionic fluxes in the initiation of the hormone secretion process. In the current report, we investigated the effects of the growth hormone (GH) secretagogues ghrelin and GH-releasing peptide-6 (GHRP-6) on the regulation of the functional expression of voltage-gated Na⁺ channels using the tumoral somatotrope GC cell line as a model. Cells were cultured under control conditions or in presence of the GH secretagogues (GHS) for 96 h, and Na⁺ currents (I_Na) were characterized in whole cell patch-clamp experiments. GHS treatment significantly increased I_Na density in a dose-dependent manner. The effects of GHRP-6 were accompanied by an augment in conductance without changes in the kinetics and the voltage dependence of the currents, suggesting an increase in the number of channels in the cell membrane. Sustained inhibition of L-type Ca²⁺ channel activity decreased I_Na density and prevented the effects of the GHS, whereas long-term exposure to an L-channel agonist increased I_Na density and enhanced the actions of GHRP-6, indicating that Ca²⁺ entry through these channels plays a role in the regulation of Na⁺ channel expression. Likewise, GHRP-6 failed to enhance Na⁺ channel expression in the presence of membrane-permeable inhibitors of protein kinases A and C, as well as the Ca²⁺/calmodulin-dependent kinase II. Conversely, treatment with a cAMP analog or a protein kinase C activator enhanced both basal and GHS-induced secretion of GH measured by enzyme-linked immunoassay, suggesting that GHRP-6 acting through the ghrelin receptor and different signaling pathways enhances Na⁺ channel membrane expression, which favors hormone release from GC somatotropes.

calcium channels; GC cells; growth hormone-releasing peptide-6; sodium channels