Characterization of two distinct depolarization-activated K+ currents in isolated adult rat ventricular myocytes.
Open Access
- 1 May 1991
- journal article
- Published by Rockefeller University Press in The Journal of general physiology
- Vol. 97 (5), 973-1011
- https://doi.org/10.1085/jgp.97.5.973
Abstract
Depolarization-activated outward K+ currents in isolated adult rat ventricular myocytes were characterized using the whole-cell variation of the patch-clamp recording technique. During brief depolarizations to potentials positive to -40 mV, Ca(2+)-independent outward K+ currents in these cells rise to a transient peak, followed by a slower decay to an apparent plateau. The analyses completed here reveal that the observed outward current waveforms result from the activation of two kinetically distinct voltage-dependent K+ currents: one that activates and inactivates rapidly, and one that activates and inactivates slowly, on membrane depolarization. These currents are referred to here as Ito (transient outward) and IK (delayed rectifier), respectively, because their properties are similar (although not identical) to these K+ current types in other cells. Although the voltage dependences of Ito and IK activation are similar, Ito activates approximately 10-fold and inactivates approximately 30-fold more rapidly than IK at all test potentials. In the composite current waveforms measured during brief depolarizations, therefore, the peak current predominantly reflects Ito, whereas IK is the primary determinant of the plateau. There are also marked differences in the voltage dependences of steady-state inactivation of these two K+ currents: IK undergoes steady-state inactivation at all potentials positive to -120 mV, and is 50% inactivated at -69 mV; Ito, in contrast, is insensitive to steady-state inactivation at membrane potentials negative to -50 mV. In addition, Ito recovers from steady-state inactivation faster than IK: at -90 mV, for example, approximately 70% recovery from the inactivation produced at -20 mV is observed within 20 ms for Ito; IK recovers approximately 25-fold more slowly. The pharmacological properties of Ito and IK are also distinct: 4-aminopyridine preferentially attenuates Ito, and tetraethylammonium suppresses predominantly IK. The voltage- and time-dependent properties of these currents are interpreted here in terms of a model in which Ito underlies the initial, rapid repolarization phase of the action potential (AP), and IK is responsible for the slower phase of AP repolarization back to the resting membrane potential, in adult rat ventricular myocytes.Keywords
This publication has 62 references indexed in Scilit:
- Molecular cloning and functional expression of a potassium channel cDNA isolated from a rat cardiac libraryFEBS Letters, 1990
- Potassium currents in cardiac cellsCellular and Molecular Life Sciences, 1987
- Cation permeation through the voltage-dependent potassium channel in the squid axon. Characteristics and mechanisms.The Journal of general physiology, 1987
- K+ Channels Gated by Voltage and IonsAnnual Review of Physiology, 1984
- Do calcium-activated potassium channels exist in the heart?Cell Calcium, 1983
- Block of outward current in cardiac Purkinje fibers by injection of quaternary ammonium ions.The Journal of general physiology, 1982
- Outward Currents in Developing Drosophila Flight MuscleScience, 1981
- A rapid technique for the isolation and purification of adult cardiac muscle cells having respiratory control and a tolerance to calciumBiochemical and Biophysical Research Communications, 1976
- Voltage clamp analysis of two inward current mechanisms in the egg cell membrane of a starfish.The Journal of general physiology, 1975
- The dynamic chloride component of membrane current in Purkinje fibersPflügers Archiv - European Journal of Physiology, 1967