| First Author | Yang SK | Year | 2008 |
| Journal | Endocrinology | Volume | 149 |
| Issue | 9 | Pages | 4726-35 |
| PubMed ID | 18535104 | Mgi Jnum | J:138159 |
| Mgi Id | MGI:3804372 | Doi | 10.1210/en.2008-0405 |
| Citation | Yang SK, et al. (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):4726-35 |
| abstractText | GHRH depolarizes the membrane of somatotropes, leading to an increase in intracellular free Ca(2+) concentration and GH secretion. Na(+) channels mediate the rapid depolarization during the initial phase of the action potential, and this regulates Ca(2+) 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, Go-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. |
