Propafenone blocks ATP-sensitive K+ channels in rabbit atrial and ventricular cardiomyocytes

Propafenone, a class I antiarrhythmic agent, inhibits several membrane currents (I-Na, I-Ca, I-K, I-to), however, its effects on ATP-sensitive potassium current (I-KATP) Of cardiac cells have not been tested. We evaluated the blocking effects of 0.1 to 100 mu M propafenone applications at 35 degrees C on the whole-cell I-KATP as triggered by dinitrophenol (75 mu M) in adult rabbit dissociated atrial and ventricular cardiomyocytes in comparison. The block of I-KATP by propafenone was dose-dependent, fully reversible and voltage-independent. The dose-response relation, as evaluated at 0 mV for atrial myocytes (ED50 = 1.26 +/- 0.17 mu M, Hill number = 1.25 +/- 0.22) was significantly shifted to the left vs. that in ventricular myocytes (ED50 = 4.94 +/- 0.59 mu M, Hill number = 1.22 +/- 0.14). It is concluded that propafenone blocks cardiac I-KATP at a single site with 4 times higher affinity for the drug in atrial myocytes. This block of cardiac I-KATP might play a role in the beneficial and adverse effects of the drug. (C) 1999 Elsevier Science B.V. All rights reserved.