{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T02:50:42Z","timestamp":1761706242571,"version":"3.35.0"},"reference-count":44,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,9,1]]},"abstract":"<jats:p>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, Go\u0308-6983 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.<\/jats:p>","DOI":"10.1210\/en.2008-0405","type":"journal-article","created":{"date-parts":[[2008,6,6]],"date-time":"2008-06-06T00:54:21Z","timestamp":1212713661000},"page":"4726-4735","source":"Crossref","is-referenced-by-count":20,"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"],"prefix":"10.1210","volume":"149","author":[{"given":"Seung-Kwon","family":"Yang","sequence":"first","affiliation":[{"name":"Prince Henry\u2019s Institute of Medical Research (S.-K.Y., K.W., C.C.), Melbourne 3168, Victoria, Australia"},{"name":"Department of Physiology (S.-K.Y., H.P.), Monash University, Melbourne 3004, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Wang","sequence":"first","affiliation":[{"name":"Prince Henry\u2019s Institute of Medical Research (S.-K.Y., K.W., C.C.), Melbourne 3168, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena","family":"Parkington","sequence":"first","affiliation":[{"name":"Department of Physiology (S.-K.Y., H.P.), Monash University, Melbourne 3004, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Chen","sequence":"first","affiliation":[{"name":"Prince Henry\u2019s Institute of Medical Research (S.-K.Y., K.W., C.C.), Melbourne 3168, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2008,6,5]]},"reference":[{"key":"2020071612253939900_R1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.2170\/jjphysiol.41.63","article-title":"Inhibition by nimodipine of growth hormone (GH) releasing factor-induced GH secretion from rat anterior pituitary cells.","volume":"41","author":"Kato","year":"1991","journal-title":"Jpn J Physiol"},{"key":"2020071612253939900_R2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/0006-8993(93)90389-5","article-title":"Human growth hormone releasing factor (hGRF) modulates calcium currents in human growth hormone secreting adenoma cells.","volume":"604","author":"Chen","year":"1993","journal-title":"Brain Res"},{"key":"2020071612253939900_R3","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1210\/endo-128-1-570","article-title":"Free intracellular Ca2+ concentration ([Ca2+]i) and growth hormone release from purified rat somatotrophs. 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