Tyrosine kinase-dependent modulation by interferon-α of the ATP-sensitive K+ current in rabbit ventricular myocytes

We examined the effects of interferon-alpha on the ATP-sensitive K+ current (IK,ATP) in rabbit ventricular cells using the patch-clamp technique. I-K,I-ATP was induced by NaCN. Whole-cell experiments indicated that interferon-alpha (5 X 10(2)-2.4 X 10(4) U/ml) inhibited I-K,I-ATP in a concentration-dependent manner (60.7+/-7.5% with 2.4X10(4) U/ml), In cell-attached configuration, interferon-alpha (2.4x10(4) U/ml) applied to the external solution also inhibited the activity of the single ATP-sensitive K+ (K-ATP) channel by 56.0 +/- 5.8% without affecting the single channel conductance. The inhibitory effect of I-K,I-ATP by interferon-alpha was blocked by genistein and herbimycin A, tyrosine-kinase inhibitors, but was not affected by N-(2-metylpiperazyl)-5-isoquinolinesulfoamide (H-7), an inhibitor of protein kinase C and cAMP-dependent protein kinase. These findings suggest that interferon-alpha inhibits the cardiac K-ATP channel through the activation of tyrosine kinase, The tyrosine kinase-mediated inhibition of I-K,I-ATP by cytokines may aggravate cell damage during myocardial ischemia, (C) 1999 Federation of European Biochemical Societies.