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(Circulation. 2001;104:2095.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Ionic Remodeling of Cardiac Purkinje Cells by Congestive Heart Failure

Wei Han, MSc; Denis Chartier, BSc; Danshi Li, MD PhD; Stanley Nattel, MD

From the Department of Medicine, Montreal Heart Institute and University of Montreal (W.H., D.C., D.L., S.N.) and the Department of Pharmacology, McGill University (W.H., S.N.), Montreal, Quebec, Canada.

Correspondence to Stanley Nattel, Montreal Heart Institute Research Center, 5000 Belanger St East, Montreal, Quebec, H1T 1C8, Canada. E-mail nattel{at}icm.umontreal.ca

Background— Cardiac Purkinje cells (PCs) are important for the generation of triggered arrhythmias, particularly in association with abnormal repolarization. The effects of congestive heart failure (CHF) on the ionic properties of PCs are unknown.

Methods and Results— PCs were isolated from false tendons of control dogs and dogs with ventricular tachypacing-induced CHF. CHF PCs were hypertrophied (capacitance, mean±SEM, 149±4 pF, n=130; versus 128±3 pF, n=150, control; P<0.001). Transient outward current density was reduced in CHF PCs without change in voltage dependence or kinetics. CHF also reduced inward-rectifier current density, with no change in form of the current-voltage relationship. Densities of L- and T-type calcium, rapid and slow delayed rectifier, and Na⁺-Ca²⁺ exchange currents were unaltered by CHF, but L-type calcium current inactivation was slowed at positive potentials. Purkinje fiber action potentials from CHF dogs showed decreased phase 1 amplitudes and elevated plateau voltages and demonstrated twice as much prolongation on exposure to the rapid delayed rectifier blocker E-4031 as control Purkinje fibers.

Conclusions— CHF causes remodeling of important K⁺ and Ca²⁺ currents in cardiac PCs, decreasing repolarization reserve and causing an exaggerated repolarization delay in response to a class III drug. These results have important potential implications regarding ventricular arrhythmogenesis, particularly related to triggered activity in PCs, in patients with CHF.

Key Words: ion channels • remodeling • electrophysiology • antiarrhythmia agents • heart failure

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