PubMed 12815169

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv1.4

Title: Corticotropin induces the expression of TREK-1 mRNA and K+ current in adrenocortical cells.

Authors: Judith A Enyeart, Sanjay Danthi, John J Enyeart

Journal, date & volume: Mol. Pharmacol., 2003 Jul , 64, 132-42

PubMed link:

Bovine adrenal zona fasciculata (AZF) cells express a two-pore/four-transmembrane segment bTREK-1 K+ channel that sets the resting potential and couples hormonal signals to depolarization-dependent Ca2+ entry and cortisol secretion. It was discovered that corticotropin (1-2000 pM) enhances the expression of bTREK-1 mRNA and membrane current in cultured AZF cells. Forskolin and 8-pcpt-cAMP mimicked corticotropin induction of bTREK-1 mRNA, but angiotensin II (AII) was ineffective. The induction of bTREK-1 mRNA by corticotropin was partially blocked by the A-kinase antagonist H-89. 8-(4-Chloro-phenylthio)-2-O-methyladenosine-3'-5'-cyclic monophosphate, a cAMP analog that activates cAMP-regulated guanine nucleotide exchange factors (Epac), failed to increase bTREK-1 mRNA. Corticotropin-stimulated increases in bTREK-1 mRNA were eliminated by inhibitors of protein synthesis or gene transcription. bTREK-1 current disappeared after 24 h in serum-supplemented medium, but in the presence of corticotropin, bTREK-1 expression was maintained for at least 48 h. The enhancement of bTREK-1 mRNA and ionic current contrasts with the corticotropin-induced down-regulation of the Kv1.4 voltage-gated K+ current and associated mRNA in AZF cells. These results demonstrate that corticotropin rapidly and potently induces the expression of bTREK-1 in AZF cells at the pretranslational level by a cAMP-dependent mechanism that is partially dependent on A-kinase but independent of Epac and Ca2+. They further indicate that prolonged stimulation of AZF cells by corticotropin, as occurs during long-term stress or disease, may produce pronounced changes in the expression of genes encoding ion channels, thereby reshaping the electrical properties of these cells to enhance or limit cortisol secretion.