DELAYED RECTIFIER CHANNELS IN HUMAN VENTRICULAR MYOCYTES

Background Previous studies have shown that in heart there are two kinetically distinct components of delayed rectifier current: a rapidly activating component (I-Kr) and a more slowly activating component (I-Ks). The presence of I-Kr and/or I-Ks appears to be species dependent. We studied the nature of the delayed rectifier current in human ventricle in whole-cell and single-channel experiments. Methods and Results Ventricular myocytes were obtained from hearts of patients with ischemic or dilated cardiomyopathy. Single-channel currents and whole-cell tail currents were recorded at negative potentials directly after return from a depolarizing step. Single-channel currents were measured in the cell-attached patch configuration with 140 mmol/L K+ in the pipette. In the present study, we identified a voltage-dependent channel with a single-channel conductance of 12.9+/-0.8 pS (mean+/-SEM, n=5) and a reversal potential near to the K+ equilibrium potential, suggesting that the channel is selective to K+ ions. Channel activity was observed only after a depolarizing step and increased with the duration and amplitude of the depolarization, indicating time- and voltage-dependent activation. Activation al +30 mV was complete within 300 milliseconds, and the time constant of activation, determined in the whole-cell configuration, was 101+/-25 milliseconds (mean+/-SEM, n=4). The voltage dependence of activation could be described by a Boltzmann equation with a half-activation potential of -29.9 mV and a slope factor of 9.5 mV. The addition of the class III antiarrhythmic drug E-4031 completely blocked channel activity in one patch. No indications for the presence of I-Ks were found in these experiments. Conclusions The conformity between the properties of I-Kr and those of the K+ channel in the present study strongly suggests that I-Kr is present in human ventricle.