REGIONAL DIFFERENCES IN I-K DENSITY IN CANINE LEFT-VENTRICLE - ROLE OF I-K,I-S IN ELECTRICAL HETEROGENEITY

Delayed rectifier K+ current (I-K) was studied in isolated myocytes from canine left ventricular epicardium and midmyocardium using whole cell patch-clamp techniques. I-K density during activation was greater in epicardial vs. midmyocardial myocytes [1.06 +/- 0.09 vs. 0.66 +/- 0.09 pA/pF (SE); P < 0.01] measured during 3-s depolarizing pulses to +25 mV. I-K density was greater in epicardial myocytes at all times examined (range 150 ms to 3 s, +25 mV) and on termination of 3-s test pulses (potentials +5 to +65 mV). Greater I-K density could not be explained by differences in activation kinetics or voltage dependence of activation. Two components of I-K (I-K,I-r and I-K,I-s) have been described in guinea pig myocytes (Sanguinetti, M. C., and N. Jurkiewicz, J. Gen. Physiol. 96: 192-214, 1990). To assess whether differences in I-K density could be ascribed to I-K,I-r or I-K,I-s, tail currents were fit to the sum of two decaying exponentials, with each component analogous to I-K,I-s and I-K,I-r based on sensitivity to E-4031 and rectification properties. Greater tail current density in epicardial myocytes was due to greater I-K,I-s with no discernible difference in I-K,I-r. These results suggest that regional differences in I-K density in left, ventricular epicardium are due to a larger I-K,I-s component, which contributes to ventricular electrical heterogeneity and may reflect the differential expression of the IsK channel.