Published Online
on July 28, 2003

A more recent version of this article appeared on August 12, 2003

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Submitted on March 6, 2003
Revised on April 18, 2003
Accepted on April 21, 2003

Ionic Remodeling of Sinoatrial Node Cells by Heart Failure

Arie O. Verkerk PhD^*, Ronald Wilders PhD, Ruben Coronel MD, PhD, Jan H. Ravesloot PhD, and E. Etienne Verheijck PhD

From the Department of Physiology (A.O.V., R.W., J.H.R., E.E.V.) and Experimental and Molecular Cardiology Group (A.O.V., R.C.), Academic Medical Center, University of Amsterdam, The Netherlands; and the Department of Cardiology (R.C.), Heart Lung Center Utrecht, Utrecht, The Netherlands.

^* To whom correspondence should be addressed. E-mail: A.O.Verkerk{at}amc.uva.nl.

Background--In animal models of heart failure (HF), heart rate decreases as the result of an increase in intrinsic cycle length of the sinoatrial node (SAN). In this study, we evaluate the HF-induced remodeling of membrane potentials and currents in SAN cells.

Methods and Results--SAN cells were isolated from control rabbits and rabbits with volume and pressure overload-induced HF and patch-clamped to measure their electrophysiological properties. HF cells were not hypertrophied (capacitance, mean±SEM, 52±3 versus 50±4 pF in control). HF increased intrinsic cycle length by 15% and decreased diastolic depolarization rate by 30%, whereas other action potential parameters were unaltered. In HF, the hyperpolarization-activated "pacemaker" current (I_f) and slow component of the delayed rectifier current (I_Ks) were reduced by 40% and 20%, respectively, without changes in voltage dependence or kinetics. T-type and L-type calcium current, rapid and ultrarapid delayed rectifier current, transient outward currents, and sodium-calcium exchange current were unaltered.

Conclusions--In single SAN cells of rabbits with HF, intrinsic cycle length is increased as the result of a decreased diastolic depolarization rate rather than a change in action potential duration. HF reduced both I_f and I_Ks density. Since I_Ks plays a limited role in pacemaker activity, the HF-induced decrease in heart rate is attributable to remodeling of I_f.

Key words: sinoatrial node • remodeling • ion channels • action potentials

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