Abnormal diastolic currents in ventricular myocytes from spontaneous hypertensive heart failure rats

1 Davis Heart and Lung Research Institute, 2 Ohio State University Biophysics Program, 3 College of Pharmacy; and 4 Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, Ohio Submitted 31 October 2005 ; accepted in final form 25 May 2006 Hypertension is a common cause of heart failure, and ventricular arrhythmias are a major cause of death in heart failure. The spontaneous hypertension heart failure (SHHF) rat model was used to study altered ventricular electrophysiology in hypertension and heart failure. We hypothesized that a reduction in the inward rectifier K + current ( I K1 ) and expression of pacemaker current ( I f ) would favor abnormal automaticity in the SHHF ventricle. SHHF ventricular myocytes were isolated at 2 and 8 mo of age and during end-stage heart failure ( 17 mo); myocytes from age-matched rats served as controls. Inward I K1 was significantly reduced at both 8 and 17 mo in SHHF rats compared with controls. There was a reduction in inward I K1 due to aging in the controls only at 17 mo. We found a significant increase in I f at all ages in the SHHF rats, compared with young controls. In controls, there was an age-dependent increase in I f . Action potential recordings in the SHHF rats demonstrated abnormal automaticity, which was abolished by the addition of an I f blocker (10 µM zatebradine). Increased I f during hypertension alone or combined increases in I f with reduced I K1 during the progression to hypertensive heart failure contribute to a substrate for arrhythmogenesis. aging; pacemaker current; inward rectifier potassium current; abnormal automaticity Address for reprint requests and other correspondence: C. A. Carnes, Ohio State Univ., College of Pharmacy, 500 W. 12th Ave., Columbus, OH 43210 (e-mail: carnes.4{at}osu.edu )