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Biophys J, May 2000, p. 2392-2404, Vol. 78, No. 5

Action Potential and Contractility Changes in [Na+]i Overloaded Cardiac Myocytes: A Simulation Study

Gregory M. Faber and Yoram Rudy

Cardiac Bioelectricity Research and Training Center and Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106-7207 USA

Sodium overload of cardiac cells can accompany various pathologies and induce fatal cardiac arrhythmias. We investigate effects of elevated intracellular sodium on the cardiac action potential (AP) and on intracellular calcium using the Luo-Rudy model of a mammalian ventricular myocyte. The results are: 1) During rapid pacing, AP duration (APD) shortens in two phases, a rapid phase without Na+ accumulation and a slower phase that depends on [Na+]i. 2) The rapid APD shortening is due to incomplete deactivation (accumulation) of IKs. 3) The slow phase is due to increased repolarizing currents INaK and reverse-mode INaCa, secondary to elevated [Na+]i. 4) Na+-overload slows the rate of AP depolarization, allowing time for greater ICa(L) activation; it also enhances reverse-mode INaCa. The resulting increased Ca2+ influx triggers a greater [Ca2+]i transient. 5) Reverse-mode INaCa alone can trigger Ca2+ release in a voltage and [Na+]i-dependent manner. 6) During INaK block, Na+ and Ca2+ accumulate and APD shortens due to enhanced reverse-mode INaCa; contribution of IK(Na) to APD shortening is negligible. By slowing AP depolarization (hence velocity) and shortening APD, Na+-overload acts to enhance inducibility of reentrant arrhythmias. Shortened APD with elevated [Ca2+]i (secondary to Na+-overload) also predisposes the myocardium to arrhythmogenic delayed afterdepolarizations.

Biophys J, May 2000, p. 2392-2404, Vol. 78, No. 5
© 2000 by the Biophysical Society   0006-3495/00/05/2392/13  $2.00


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