Delayed rectifier K currents have reduced amplitudes and altered kinetics in myocytes from infarcted canine ventricle

Objective: The rapid (I-Kr) and slow (I-Ks) components of delayed rectifier currents play an important role in determining the cardiac action potentia l configuration. Abnormalities in their function may contribute to arrhythm ogenesis under pathological conditions. We studied the effects of myocardia l infarction on I-Kr and I-Ks in canine ventricular myocytes and their mole cular basis. Methods: Infarct zone myocytes (IZs) were isolated from a thin layer of surviving epicardium overlying an infarct 5 days after a total oc clusion of the left anterior descending (LAD) coronary artery. Normal myocy tes (NZs) were isolated from the corresponding region of control hearts for comparison. Currents were recorded under the whole-cell patch clamp condit ions. Results: Both I-Kr and I-Ks current densities were reduced in IZs ver sus NZs. Kinetic analysis further suggests an acceleration of I-Kr activati on and I-Ks deactivation. RNase protection assays were used to quantify the mRNA levels of I-Kr and I-Ks channel subunits (dERG, dIsK and dKvLQT1) in tissue immediately adjacent to the region where myocytes were isolated, mRN A levels of all three subunits were reduced 2 days after LAD occlusion (by 48+/-9%, 68+/-5%, and 45+/-4% for dERG, dIsK and dKvLQT1, respectively, n=8 each). By day 5, the dKvLQT1 message returned to control while those of dE RG and dIsK remained reduced (by 52+/-7% and 76+/-6%, respectively). Conclu sions: The decrease in I-Kr and I-Ks amplitudes and changes in their kineti cs in infarcted tissue might be due to a decrease in functional channels an d/or changes in their subunit composition. Heterogeneous changes in I-Kr an d I-Ks in infarcted hearts may impact on the effects of varying heart rate or neurohumoral modulation on repolarization. (C) 2000 Elsevier Science B.V . All rights reserved.