Role of kinases and G-proteins in the hyposmotic stimulation of cardiac I(Ks).
Exposure of cardiac myocytes to hyposmotic solution stimulates slowly-activating delayed-rectifying K(+) current (I(Ks)) via unknown mechanisms. In the present study, I(Ks) was measured in guinea-pig ventricular myocytes that were pretreated with modulators of cell signaling processes, and then exposed to hyposmotic solution. Pretreatment with compounds that (i) inhibit serine/threonine kinase activity (10-100 muM H89; 200 muM H8; 50 muM H7; 1 muM bisindolylmaleimide I; 10 muM LY294002; 50 muM PD98059), (ii) stimulate serine/threonine kinase activity (1-5 muM forskolin; 0.1 muM phorbol-12-myristate-13-acetate; 10 muM acetylcholine; 0.1 muM angiotensin II; 20 muM ATP), (iii) suppress G-protein activation (10 mM GDPbetaS), or (iv) disrupt the cytoskeleton (10 muM cytochalasin D), had little effect on the stimulation of I(Ks) by hyposmotic solution. In marked contrast, pretreatment with tyrosine kinase inhibitor tyrphostin A25 (20 muM) strongly attenuated both the hyposmotic stimulation of I(Ks) in myocytes and the hyposmotic stimulation of current in BHK cells co-expressing Ks channel subunits KCNQ1 and KCNE1. Since attenuation of hyposmotic stimulation was not observed in myocytes and cells pretreated with inactive tyrphostin A1, we conclude that TK has an important role in the response of cardiac Ks channels to hyposmotic solution.[1]References
- Role of kinases and G-proteins in the hyposmotic stimulation of cardiac I(Ks). Missan, S., Linsdell, P., McDonald, T.F. Biochim. Biophys. Acta (2006) [Pubmed]
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