DOES TYROSINE KINASE MODULATE DELAYED-RECTIFIER K-CHANNELS IN GUINEA-PIG VENTRICULAR CELLS

Phosphorylation by tyrosine kinases has been shown to promote cellular growth and hypertrophy and to play a key role in modulating ion chann els. We have examined possible effects of genistein, a protein tyrosin e kinase (PTK) inhibitor, on cardiac delayed-rectifier K currents (I-K ). Guinea pig ventricular were voltage-clamped by conventional mode (5 .4 mM [K](out)/150 mM [K](in); pCa = 8; 36 degrees C). Amplitudes of t ail and steady-state (2-s pulse) currents were measured as I,. Micromo lar concentrations of genistein (10-100 mu M) reversibly inhibited bas al, swelling-enhanced (by 70% hypotonic solution), and intrapipette Cy clic adenosine monophosphate (cAMP) (1 mM)-enhanced I-K concentration- dependently, while intrapipette cAMP-enhanced I-K were also affected b y daidzein, an inactive analog of genistein. In contrast, lavendustin A (10 mu M) and tyrphostin 51. (100 mu M), other types of PTK inhibito rs, had no effect on I-K. These results suggest that genistein may inh ibit I-K and that this inhibition is not mediated by an inhibition of tyrosine kinase activity.