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Cardiovascular Research 1997 33(3):540-547; doi:10.1016/S0008-6363(96)00221-0
© 1997 by European Society of Cardiology
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Copyright © 1997, European Society of Cardiology

Electrophysiological and pharmacological correspondence between Kv4.2 current and rat cardiac transient outward current

Sarita W. Yeola1 and Dirk J. Snyders*

Departments of Medicine and Pharmacology, 554-MRB2, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA

Objective: The transient outward current (ITO) plays an important role in early repolarization and overall time course of the cardiac action potential. At least two K+ channel {alpha}-subunits cloned from cardiac tissue (Kv1.4 and Kv4.2) encode rapidly inactivating channels. The goal of this study was to determine functional and pharmacological properties of Kv4.2 expressed in mammalian cells, especially those that would differentiate between both isoforms in comparison to native ITO. Methods: Both Kv4.2 and Kv1.4 isoforms were stably expressed in mouse L-cell lines, and expressed currents were studied using whole-cell voltage clamp techniques. Results: The expressed Kv4.2 currents displayed fast inactivation with a half-inactivation potential of –41 mV. Recovery from inactivation was rapid ({tau}recov = 160 ms at –90 mV) and strongly voltage-dependent. Flecainide (10 µM) had minimal effects on Kv1.4 currents, but reduced Kv4.2 peak current by 53% and increased the apparent rate of inactivation consistent with open channel block. Quinidine (10–20 µM) reduced the peak current and accelerated the apparent rate of inactivation in both isoforms. The Kv4.2 current displayed use-dependent unblock in the presence of 4-AP. Conclusions: The functional properties of Kv4.2, especially the flecainide sensitivity, resemble those of ITO in rat (and human) myocytes better than those of Kv1.4. These results provide the necessary functional support for the hypothesis that Kv4.2 is a major isoform contributing to cardiac ITO, consistent with independent biochemical and molecular evidence that indicates that Kv4.2 is readily detected in rat myocytes.

KEYWORDS Potassium channels; Potassium channels, transient outward; Ion channel; Quinidine; Flecainide; 4-Aminopyridine

1 Present address: Department of Physiology and Biophysics, SUNY, Stony Brook, NY 11794-8661.

* Corresponding author. Tel. +1615 936-1680; Fax +1 615 322-4707. dirk.snyders{at}mcmail.vanderbilt.edu


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