Referenced in: none

Automatically associated channels: ClC4

Title: [Regulation of the drug-sensitivity of anion channels via phosphorylation]

Authors: Jun Yamazaki, Kenji Kitamura

Journal, date & volume: Nippon Yakurigaku Zasshi, 2003 Nov , 122 Suppl, 67P-70P

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/14727526

Abstract
Chloride channels in mammalian cell membranes play an important role in cell homeostasis. The Cl- channels that have been identified as molecular entities are CFTR, CLC, CLCA, etc. We focused on two types of these channels and investigated their modulatory mechanism. (i) Endothelin-activated oscillatory Cl- currents in the smooth muscle cells of the microvasculature have been shown to be attributable to Ca2+ released from intracellular stores. These currents were inhibited by protein kinase (PK) A activation by agents such as forskolin and prostacyclin. Since overexpressed CLCA Cl- channels newly cloned from rats were directly suppressed by forskolin Ca(2+)-activated Cl- channels are likely to be modulated by PKA-mediated phosphorylation in an inhibitory manner. (ii) A CFTR isoform is known to be expressed in myocardial cells and to participate in the regulation of cell excitability. In Xenopus oocytes expressing the isoform, the Cl- current was found to be activated by PKA-mediated phosphorylation. In experiments using inhibitors of phosphorylation and dephosphorylation, the PKA-mediated effect was shown to be regulated by the phosphorylated states modulated by PKC endogenously. These results suggest that the Cl- channel activity may be influenced by the basal phosphorylated states modulated by different types of kinases in addition to the main regulatory pathway.