Characterization of two distinct depolarization-activated K+ currents in isolated adult rat ventricular myocytes

Michael Apkon, Jeanne M. Nerbonne

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277 Scopus citations

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, Ca2+-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 ≈ 10-fold and inactivates ≈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: I+ 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, ≈ 70% recovery from the inactivation produced at -20 mV is observed within 20 ms for Ito; IK recovers ≈ 25-fold more slowly. The pharmacological properties of Ito and I s are also distinct: 4-aminopyridine preferentially attenuates Ito, and tetraethylammonium suppresses predominantly I s. 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.

Original languageEnglish
Pages (from-to)973-1011
Number of pages39
JournalJournal of General Physiology
Volume97
Issue number5
DOIs
StatePublished - May 1 1991

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