Characteristics of I(K) and its response to quinidine in experimental healed myocardial infarction.

Abstract

Mechanisms and drug treatment of serious ventricular arrhythmias in patients with healed myocardial infarction (HMI) are incompletely understood, in part because the electrophysiology and pharmacology of myocytes from noninfarcted regions of HMI hearts are not well characterized. We studied the delayed rectifier potassium current (I(K)) and quinidine responsiveness of single left ventricular subendocardial myocytes isolated from the region remote to the border zone of healed infarct myocardium (4 to 6 mm from scar edge) in cat hearts 2 months after coronary artery occlusion. Subendocardial cells isolated from corresponding regions of normal cat hearts provided controls. I(K) activation and tail currents were recorded using whole cell, voltage clamp techniques. Membrane capacitance of cells remote to HMI (187 +/- 7 pF) was significantly greater than normal (155 +/- 6 pF; P < 0.001). Action potential durations (APDs) recorded from myocytes in remote regions were prolonged (APD90 = 247 +/- 10 msec) compared to normal (214 +/- 11 msec; P < 0.05). Quinidine (1 microM) significantly prolonged APD90 in normal cells but not in remote cells. Density of I(K) (tail current) was significantly decreased in remote cells (3.1 +/- 0.3 pA/pF) compared to normal (3.9 +/- 0.3 pA/pF; P < 0.05), and voltage-dependent activation of I(K) was shifted in the positive direction. Quinidine had significantly less incremental blocking effect on I(K) already blunted by regional hypertrophy compared to its effect on normal cells in remote cells. IC50 shifted to 0.95 microM in remote cells compared with 0.50 microM in normal cells. Cells in noninfarct region remote from the scar are hypertrophied and display altered electrophysiology. Their reduced I(K) responsiveness to quinidine may explain, in part, failure of quinidine to prolong APD in such cells. Moreover, dispersion of repolarization may be decreased by the effect of quinidine on normal cells.