|
|
||||||||
1Davis Heart and Lung Research Institute, 2Ohio State University Biophysics Program, 3College of Pharmacy; and 4Department 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 (IK1) and expression of pacemaker current (If) 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 IK1 was significantly reduced at both 8 and
17 mo in SHHF rats compared with controls. There was a reduction in inward IK1 due to aging in the controls only at
17 mo. We found a significant increase in If at all ages in the SHHF rats, compared with young controls. In controls, there was an age-dependent increase in If. Action potential recordings in the SHHF rats demonstrated abnormal automaticity, which was abolished by the addition of an If blocker (10 µM zatebradine). Increased If during hypertension alone or combined increases in If with reduced IK1 during the progression to hypertensive heart failure contribute to a substrate for arrhythmogenesis.
aging; pacemaker current; inward rectifier potassium current; abnormal automaticity
This article has been cited by other articles:
![]() |
V. A. Lacombe, S. Viatchenko-Karpinski, D. Terentyev, A. Sridhar, S. Emani, J. D. Bonagura, D. S. Feldman, S. Gyorke, and C. A. Carnes Mechanisms of impaired calcium handling underlying subclinical diastolic dysfunction in diabetes Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2007; 293(5): R1787 - R1797. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |