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Involvement of Tyrosine Kinase in the Hyposmotic Stimulation of I Ks in Guinea-pig Ventricular Myocytes

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Journal Pflugers Arch
Specialty Physiology
Date 2007 Dec 22
PMID 18097684
Citations 3
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Abstract

The objective of this study was to investigate the involvement of tyrosine phosphorylation in the hyposmotic stimulation of cardiac I Ks, a slowly activating delayed-rectifier K+ current that promotes repolarization of the action potential. The current was recorded from whole-cell-configured guinea-pig ventricular myocytes before, during, and after their exposure to solution whose osmolarity was 0.75 times normal. Exposure to hyposmotic solution caused a near-doubling of the amplitude of I Ks, with little change in the voltage dependence of current activation. Stable, hyposmotically stimulated I Ks (I Ks,Hypo) was decreased by broadspectrum tyrosine kinase (TK) inhibitors tyrphostin A23 (IC50 approximately 5 microM) and tyrphostin A25 (IC50 15.8 +/- 1.6 microM) but not by TK-inactive tyrphostin analogs, suggesting that tyrosine phosphorylation is important for maintenance of the current. In agreement with that view, we found that the TK-inhibitor action on I Ks,Hypo was strongly antagonized by vanadate compounds known to inhibit phosphotyrosyl phosphatase. When myocytes were pretreated with TK inhibitors, the stimulation of I Ks was attenuated in a concentration-dependent manner. The attenuation was not due to concomitant attenuation of a stimulation of tyrosine phosphorylation because neither the stimulation of I Ks nor its rate of decay following removal of hyposmotic solution was affected by pretreatment with vanadates. We suggest that the stimulation of I Ks by hyposmotic solution is dependent on a basal tyrosine phosphorylation that modulates a swelling-induced I Ks-stimulatory signal and/or the receptivity of Ks channels to that signal.

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