Properties of the transient outward current in rabbit atrial cells.

Abstract

1. Whole-cell and patch clamp techniques have been used to study the steady-state voltage dependence and the kinetics of a transient outward current. It, in single cells from rabbit atrium. 2. The steady-state voltage dependence of both activation and inactivation of It are well described by Boltzmann functions. Inactivation is fully removed at potentials negative to -70 mV and it is complete near 0 mV. The threshold for activation of It is near -30 mV and it is fully activated at +30 mV. The region of overlap between the activation and inactivation curves indicates that a steady non-inactivating current will be recorded over a membrane potential range from approximately -30 to 0 mV. 3. In general, the time course of inactivation at potentials in the range 0 to +50 mV is best described as a sum of two exponential functions. The kinetic parameters controlling these processes exhibit only very weak voltage dependence. 4. Comparison of the time course of the development of inactivation in response to long depolarizing voltage clamp steps with the development of inactivation in response to trains of brief depolarizing pulses indicates that inactivation develops very quickly and decays relatively slowly at potentials near the resting potential (e.g. -70 mV). Thus, in response to (i) a train of voltage-clamp pulses or (ii) a series of action potentials, the magnitude of It decreases due to a progressive increase in the amount of inactivation. 5. A simple model of channel gating is presented: it can account for the major aspects of the voltage dependence and kinetics of It (cf. Aldrich, 1981). 6. Cell-attached patch clamp recordings have been used to identify the single-channel or unitary events underlying the current, It. In general, only one active channel is present per patch. The single-channel conductance in normal Tyrode solution is approximately 14 pS and the current-voltage relationship is approximately linear between +50 and +150 mV with respect to rest. This information in combination with the fully activated current-voltage characteristics from the whole-cell data, can be used to estimate the number and density of It channels per cell: these are 1600 and one pr 3-4 .mu.m2, respectively. 7. Ensemble averages obtained from patch recordings are very similar in time course to the macroscopic or whole-cell current itself: the ensemble current rises to a peak within approximately 5 ms and decays with a biexponential time course in response to depolarizations to approximately +50 mV. 8. Application of repetitive depolarizing clamp pulses to patches containing active channels shows that the probability depolarizing clamp pulses to patches containing active channels shows that the probability of a channel being open decreases significantly with repetitive depolarizations. This kinetic property may explain the decrease in macroscopic current observed during repetitive trains of depolarizations. The microscopic properties of It which have been identified in this study can be used to develop more detailed electrophysiological models of early repolarization in mammalian myocardium and, in addition, will be of importance in determining the mechanism of certain drug- (e.g. quinidine) induced changes in repolarization.