Potassium rectifier currents differ in myocytes of endocardial and epicardial origin

Whole-cell voltage-clamp experiments and single-channel current recordings in cell-attached patch mode were performed on enzymatically dissociated single ventricular myocytes harvested from feline endocardial and epicardial surfaces. The studies were designed to compare the characteristics of inward rectifier K⁺ current (I_K1) and delayed rectifier K⁺ current (I_K) between endocardial and epicardial cells and to test the hypothesis that the differential characteristics of I_K1 and/or I_K are responsible for the differences in action potential configuration between the two cell types. I_K1 in endocardial cells displayed a distinct N-shaped current-voltage (I-V) relation, with a prominent outward current at potentials between -80 and -30 mV. In epicardial cells, an outward current region was much smaller, and the I-V relation demonstrated a blunted N-shaped I-V relation. In single-channel current recordings in cell-attached patch mode, neither unitary current amplitude of I_K1 nor probability of channel opening was different between endocardial and epicardial cells, suggesting that the difference in the number of functional channels might be responsible for the differential I_K1 I-V relations. The characteristics of I_K also differed between endocardial and epicardial cells. The time course of growth of tail current of I_K (I_K,tail) (activation of I_K) was significantly enhanced and that of I_K,tail deactivation was delayed in epicardial cells compared with endocardial cells. The time constant of the slow component of I_K activation at +20 mV was 3,950±787 msec in endocardial cells and 2,746±689 msec in epicardial cells (P<0.05); the corresponding values for I_K deactivation at -50 mV were 1,041±387 msec and 1,959±551 msec, respectively (p<0.01). The voltage dependence of steady-state activation of I_K,tail was similar between endocardial and epicardial cells, suggesting that the probability of channel opening at any potential was not different in the two cell types. The amplitude and density of fully activated I_K (I_K,full) were significantly greater in epicardial cells than in endocardial cells. At repolarization to -20 mV, I_K,full amplitude was 452±113 pA in endocardial cells and 578±135 pA in epicardial cells (P<0.05), and the corresponding values for I_K,full density were 2.86±0.73 and 4.21±0.83 μA/cm², respectively (p<0.05). A nonstationary fluctuation analysis revealed that the amplitude of I_K unitary current was similar between endocardial and epicardial cells (0.23±0.07 versus 0.22±0.03 pA, p=NS). Thus, the difference in whole-cell current amplitude of I_K might be due to the difference in the number of functional channels per myocyte. These data lead us to suggest that the differential characteristics of I_K1 and I_K contribute to the difference of action potential configuration between endocardial and epicardial cells.