(Circulation. 1995;92:3497-3504.)
© 1995 American Heart Association, Inc.
Articles |
Delayed Rectifier Channels in Human Ventricular Myocytes
From the Department of Physiology (M.W.V., A.C.G.vG., L.N.B.), Academic Medical Center, and the Department of Clinical and Experimental Cardiology (T.O.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Correspondence to Marieke W. Veldkamp, Department of Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Background Previous studies have shown that in heart there are two kinetically distinct components of delayed rectifier current: a rapidly activating component (IKr) and a more slowly activating component (IKs). The presence of IKr and/or IKs 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 at +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 IKs were found in these experiments.
Conclusions The conformity between the properties of IKr and those of the K+ channel in the present study strongly suggests that IKr is present in human ventricle.
Key Words: ventricles • potassium • delayed rectifyer current
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