Role of tyrosine kinase activity in cardiac slow delayed rectifier channel modulation by cell swelling.

Abstract

We studied the effects of cell swelling on membrane currents of canine ventricular myocytes using the whole-cell patch-clamp method. Cell swelling was induced by lowering the osmolarity of the bath solution to 60% of control. Cell width and currents were measured simultaneously. Cell swelling induced little or no change in the L-type Ca, the inward rectifier, and the transient outward currents, but a marked increase in the slow delayed rectifier current (IKs) was seen. We further examined the role of protein kinase activities in IKs modulation by cell swelling. This modulation was not affected by inhibiting serine/threonine kinases using H-8. On the other hand, the modulation was inhibited by genistein (a protein tyrosine kinase inhibitor) although not by daidzein (an inactive analogue of genistein). Our data suggest that in canine ventricle cell swelling can increase protein tyrosine kinase activity, which can augment IKs and contribute to changes in membrane electrical activity observed under these conditions.