Regional differences in IK density in canine left ventricle: role of IK,s in electrical heterogeneity

Delayed rectifier K+ current (IK) was studied in isolated myocytes from canine left ventricular epicardium and midmyocardium using whole cell patch-clamp techniques. IK 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. IK 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 IK density could not be explained by differences in activation kinetics or voltage dependence of activation. Two components of IK (IK,r and IK,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 IK density could be ascribed to IK,r or IK,s, tail currents were fit to the sum of two decaying exponentials, with each component analogous to IK,s and IK,r based on sensitivity to E-4031 and rectification properties. Greater tail current density in epicardial myocytes was due to greater IK,s with no discernible difference in IK,r. These results suggest that regional differences in IK density in left ventricular epicardium are due to a larger IK,s component, which contributes to ventricular electrical heterogeneity and may reflect the differential expression of the IsK channel.