Pacing-induced heart failure causes a reduction of delayed rectifier potassium currents along with decreases in calcium and transient outward currents in rabbit ventricle

Objective: Heart failure in patients and in animal models is associated wit h action potential prolongation of the ventricular myocytes. Changes in sev eral membrane currents have been already demonstrated to underlie this prol ongation. However, information on the two components (I-Kr and I-Ks) of the delayed rectifier potassium current (I-K) in rapid pacing induced heart fa ilure is lacking. Methods and results: Action potentials and whole-cell cur rents, I-K, I-tol, I-Kl, and ICa-L were recorded in apical myocytes of left ventricle from 10 rabbits subjected to left ventricular pacing at 350-380 beats/min for 3-4 weeks and 10 controls with shan operation. Action potenti al duration at 90% repolarization (APD(90)) was prolonged in myocytes from failing hearts compared to controls at both cycle lengths of 333 and 1000 m s. Both E-4031-sensitive and -resistant components of I-K (I-Kr, I-Ks) in m yocytes from failing hearts were significantly less than those of control h earts; tail current densities of I-Kr and I-Ks following depolarization to +50 mV were 0.62+/-0-05 vs. 0.96+/-0.12 pA/pF (P<0.05), and 0.27+/-0.08 vs. 0.52+/-0.08 pA/pF (P<0.05), respectively. There was no significant differe nce between control and failing myocytes in the voltage- and time-dependenc e of activation of total I-K, I-Kr and I-Ks. The peak of L-type Ca2+ curren t (ICa-L) was significantly reduced in myocytes from failing hearts (at +10 mV, -9.29+/-0.52 vs. -12.28+/-1.63 pA/pF, P<0.05), as was the Ca2+-indepen dent transient outward current (I-tol; at +40 mV,4.8+/-0.9 vs. 9.6+/-1.3 pA /pF, P<0.05). Steady state I-V curve for I-Kl was similar in myocytes from failing and control hearts. Conclusions: Decrease of I-K (both I-Kr and I-K s) in addition to reduced I-tol, may underly action potential prolongation at physiological cycle length and thereby contribute to arrhythmogenesis in heart failure. (C) 2000 Elsevier Science B.V. All rights reserved.