Electrophysiological and pharmacological correspondence between Kv4.2 current and rat cardiac transient outward current.
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 microM) 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 microM) 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.
Yeola
S W
SW
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA.
Snyders
D J
DJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002460:Cell Line; D005424:Flecainide / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D006801:Humans; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011802:Quinidine / Q000494:pharmacology; D051381:Rats; D051672:Shal Potassium Channels
D000889:Anti-Arrhythmia Agents; C497018:KCND2 protein, human; D015221:Potassium Channels; D051672:Shal Potassium Channels; D011802:Quinidine; D005424:Flecainide