Involvement of tetrodotoxin-resistant Na+ current and protein kinase C in the action of growth hormone (GH)-releasing hormone on primary cultured somatotropes from GH-green fluorescent protein transgenic mice

Yang, Seung Kwon, Wang, Kun, Parkington, Helena and Chen, Chen (2008) Involvement of tetrodotoxin-resistant Na+ current and protein kinase C in the action of growth hormone (GH)-releasing hormone on primary cultured somatotropes from GH-green fluorescent protein transgenic mice. Endocrinology, 149 9: 4726-4735. doi:10.1210/en.2008-0405


Author Yang, Seung Kwon
Wang, Kun
Parkington, Helena
Chen, Chen
Title Involvement of tetrodotoxin-resistant Na+ current and protein kinase C in the action of growth hormone (GH)-releasing hormone on primary cultured somatotropes from GH-green fluorescent protein transgenic mice
Formatted title
Involvement of tetrodotoxin-resistant Na+ current and protein kinase C in the action of growth hormone (GH)-releasing hormone on primary cultured somatotropes from GH-green fluorescent protein transgenic mice
Journal name Endocrinology   Check publisher's open access policy
ISSN 0013-7227
1945-7170
Publication date 2008-09
Year available 2008
Sub-type Article (original research)
DOI 10.1210/en.2008-0405
Volume 149
Issue 9
Start page 4726
End page 4735
Total pages 8
Place of publication Chevy Chase, MD, United States
Publisher The Endocrine Society
Collection year 2009
Language eng
Subject C1

110306 Endocrinology
970106 Expanding Knowledge in the Biological Sciences
Formatted abstract
GHRH depolarizes the membrane of somatotropes, leading to an increase in intracellular free Ca2+ concentration and GH secretion. Na+ channels mediate the rapid depolarization during the initial phase of the action potential, and this regulates Ca2+ influx and GH secretion. GHRH increases a tetrodotoxin-sensitive somatotrope Na+ current that is mediated by cAMP. TTX-resistant (TTX-R) Na+ channels are abundant in sensory neurons and cardiac myocytes, but their occurrence and/or function in somatotropes has not been investigated. Here we demonstrate expression of TTX-R Na+ channels and a TTX-R Na+ current, using patch-clamp method, in green fluorescent protein-GH transgenic mouse somatotropes. GHRH (100nm) increased the TTX-R Na+ current in a reversible manner. The GHRH-induced increase in TTX-R Na+ current was not affected by the cAMP antagonist Rp-cAMP or protein kinase A inhibitors KT5720 or H89. The TTX-R current was increased by 8-bromoadenosine-cAMP (cAMP analog), forskolin (adenylyl-cyclase activator), and 3-isobutyl-1-methylxanthine (phosphodiesterase inhibitor), but the additional, GHRH-induced increase in TTX-R Na+ currents was not affected. U-73122 (phospholipase C inhibitor) and protein kinase C (PKC) inhibitors, Gö-6983 and chelerythrine, blocked the effect of GHRH. PKC activators, phorbol dibutyrate and phorbol myristate acetate, increased the TTX-R Na+ current, but GHRH had no further effect on the current. Na+-free extracellular medium significantly reduced GHRH-stimulated GH secretion. We conclude that GHRH-induced increase in the TTX-R Na+ current in mouse somatotropes is mediated by the PKC system. An increase in the TTX-R Na+ current may contribute to the GHRH-induced exocytosis of GH granules from mouse somatotropes.
Keyword RAT PITUITARY-CELLS
VOLTAGE-GATED NA+
SODIUM-CHANNELS
SENSORY
NEURONS
SKELETAL-MUSCLE
TRANSDUCTION PATHWAYS
EXTRACELLULAR NA+
ACTION-POTENTIALS
CALCIUM CURRENTS
DRG NEURONS
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Biomedical Sciences Publications
 
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Created: Wed, 18 Mar 2009, 12:02:16 EST