Delayed rectifier potassium current in undiseased human ventricular myocytes

Objective: The purpose of the study was to investigate the properties of the delayed rectifier potassium current (I-K) in myocytes isolated from undiseased human left ventricles. Methods: The whole-cell configuration of the patch-clamp technique was applied in 28 left ventricular myocytes from 13 hearts at 35 degrees C. Results: An E-4031 sensitive tail current identified the rapid component of I-K (I-Kr) in the myocytes, but there was no evidence for an E-4031 insensitive slow component of I-K (I-Kb). When nifedipine (5 mu M) was used to block the inward calcium current (I-Ca), I-Kr activation was fast (tau=31.0+/-7.4 ms, at +30 mV, n=5) and deactivation kinetics were biexponential and relatively slow (tau(1) =600.0+/-53.9 ms and tau(2)-6792.2+/-875.7 ms, at -40 mV, n=7). Application of CdCl2 (250 mu M) to block I-Ca altered the voltage dependence of the I-Kr considerably, slowing its activation (tau=657.1+/-109.1 ms, at +30 mv n=5) and accelerating its deactivation ( tau=104.0+/-18.5 ms, at -40 mV, n=8). Conclusions: In undiseased human ventricle at 35 degrees C I-Kr exists having fast activation and slow deactivation kinetics; however, there was no evidence found for an expressed I-Ks. I-Kr probably plays an important role in the frequency dependent modulation of repolarization in undiseased human ventricle, and is a target for many Class III antiarrhythmic drugs. (C) 1998 Elsevier Science B.V. All rights reserved.