Rapid inward current in ischemically-injured subepicardial myocytes bordering myocardial infarction

To determine if collagenase-dispersed epicardial myocytes overlying myocardial infarction reproduce the same altered electrophysiology observed in intact epicardium, multicellular tissue preparations and enzymatically-dispersed myocytes from ischemically-injured canine subepicardium were examined 1 and 4 days after myocardial infarction.

The electrophysiologic changes observed with ischemic injury in enzymatically-dispersed myocytes were not different from changes observed in multicellular tissue preparations at 1 and 4 days postinfarction. Ischemically-injured myocytes were depolarized versus normal myocytes at [K0]+ (2.5 to 40 mM) with reduced membrane potentials also observed in injured subepicardial tissue preparations [K0]+ (4 to 24 mM). On day 1, the reduced Vmax and the prolonged recovery of Vmax from inactivation were consistent with the reduced membrane potentials observed at each [K0]+. The half-maximal Vmax, maximal Vmax, and Boltzmann constant (k) in injured myocytes were unchanged versus normal myocytes. On day 4 postinfarction, the half-maximal Vmax was shifted to a more negative membrane potential, the maximal Vmax was reduced, and k was increased in injured versus normal myocytes. Prolonged recovery from inactivation was observed with depressed membrane potentials in injured myocytes on day 4.

Enzymatically-dispersed myocytes from ischemically-injured subepicardium closely reproduce altered cellular properties observed in multicellular tissue preparations. The data suggest that 1 day postinfarction, altered conduction and refractoriness largely result from a reduced membrane potential. At 4 days, a reduced maximal Vmax, a shift in the inactivation curve to more negative voltages, and prolonged recovery of Vmax from inactivation also contribute to slowed conduction and prolonged refractoriness.