抄録
α1-adrenergic modulation of volume-regulated chloride current (ICl,vol) was examined in mouse ventricular myocytes with the whole-cell patch clamp. Phenylephrine (PE), an α1-adrenergic agonist, inhibited the hypotonicity-induced activation of ICl,vol. The inhibition did not occur in the presence of prazosin, an α1-adrenergic antagonist, or in the cells dialyzed with anti-Gq/11 antibody. U-73122, a phospholipase C inhibitor, prevented the PE-induced inhibition of ICl,vol, whereas bisindolylmaleimide-I, a protein kinase C inhibitor, was without effect. Interestingly, PE did not affect ICl,vol in the cells loaded with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and the intracellular application of anti-PI(4,5)P2 antibody reduced the amplitude of ICl,vol in control cells. Furthermore, the activation of ICl,vol was suppressed by application of wortmannin (WMN), which is an inhibitor of phophatidylinositol kinases, and thus is expected to prevent re-synthesis of membrane PI(4,5)P2. However, the inhibition of ICl,vol by WMN persisted after additional intracellular application of PI(4,5)P2. Considering that cell-swelling may activate phosphatidylinositol 3-kinase (PI3K) which is sensitive to WMN, we hypothesize that certain phospholipid component(s) converted from membrane PI(4,5)P2 by the activated PI3K play an essential role in the activation of cardiac ICl,vol, and that α1-adrenergically induced depletion of membrane PI(4,5)P2 level leads to inhibition of ICl,vol. [J Physiol Sci. 2008;58 Suppl:S80]
