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°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 Ks). When nifedipine (5 μM) was used to block the inward calcium current ( I Ca), I Kr activation was fast ( τ =31.0±7.4 ms, at +30 mV, n =5) and deactivation kinetics were biexponential and relatively slow ( τ 1 =600.0±53.9 ms and τ 2=6792.2±875.7 ms, at −40 mV, n =7). Application of CdCl2 (250 μM) to block I Ca altered the voltage dependence of the I Kr considerably, slowing its activation ( τ =657.1±109.1 ms, at +30 mV, n =5) and accelerating its deactivation ( τ =104.0±18.5 ms, at −40 mV, n =8). Conclusions: In undiseased human ventricle at 35°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.