© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Functional expression of an inactivating potassium channel (Kv4.3) in a mammalian cell line
aDepartments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA
bInstitute of Pharmacology and Toxicology, CSIC School of Medicine, Universidad Complutense, 28040 Madrid, Spain
cLaboratory for Molecular Biophysics, Physiology and Pharmacology, University of Antwerpen (UIA), B-2610 Wilrijk, Belgium
* Corresponding author. Tel.: +34-91-394-1474; fax: +34-91-394-1470; e-mail: carmenva@eucmax.sim.ucm.es
Objective: The goal of this study was to characterize the electrophysiological properties of the Kv4.3 channels expressed in a mammalian cell line. Methods: Currents were recorded using the whole-cell voltage clamp technique. Results: The threshold for activation of the expressed Kv4.3 current was approximately –30 mV. The dominant time constant for activation was 1.71±0.16 ms (n=10) at +60 mV. The current inactivated, this process being incomplete, resulting in a sustained level which contributed 15±2% (n=25) of the total current. The time course of inactivation was fit by a biexponential function, the fast component contributing 74±5% (n=9) to the overall inactivation. The fast time constant was voltage-dependent [27.6±2.0 ms at +60 mV (n=10) versus 64.0±3.6 ms at 0 mV (n=10); P<0.01], whereas the slow was voltage-independent [142±15 ms at +60 mV (n=10) versus 129±33 ms at 0 mV (n=6) P>0.05]. The voltage-dependence of inactivation exhibited midpoint and slope values of –26.9±1.5 mV and 5.9±0.3 mV (n=21). Recovery from inactivation was faster at more negative membrane potentials [203±17 ms (n=13) and 170±19 ms (n=4), at –90 and –100 mV]. Bupivacaine block of Kv4.3 channels was not stereoselective (KD
31 µM). Conclusions: The functional profile of Kv4.3 channels expressed in Ltk– cells corresponds closely to rat ITO, although differences in recovery do not rule out association with accessory subunits. Nevertheless, the sustained component needs to be considered with respect to native ITO.
KEYWORDS K-channels; Ion channels; Membrane currents; Antiarrhythmic agents; Arrhythmia
1 Present address: Department of Physiology, Colorado State University, Fort Collins, CO 80523, USA
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