(Circulation. 2000;102:2137.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Enhanced Ca2+ Release and Na/Ca Exchange Activity in Hypertrophied Canine Ventricular Myocytes
Potential Link Between Contractile Adaptation and Arrhythmogenesis
From the Laboratory of Experimental Cardiology (K.R.S., F.v.d.W.) and Department of Physiology (F.V.), University of Leuven, Belgium, and the Department of Cardiology, Academic Hospital Maastricht (P.G.A.V., S.H.M.d.G., H.J.J.W., M.A.V.), Netherlands.
Correspondence to Karin R. Sipido, MD, PhD, Laboratory of Experimental Cardiology, KUL, Campus Gasthuisberg O/N, Herestraat 49, B-3000 Leuven, Belgium. E-mail karin.sipido{at}med.kuleuven.ac.be
Background—Ventricular arrhythmias are a major cause of sudden death in patients with heart failure and hypertrophy. The dog with chronic complete atrioventricular block (CAVB) has biventricular hypertrophy and ventricular arrhythmias and is a useful model to study underlying cellular mechanisms. We investigated whether changes in Ca2+ homeostasis are part of the contractile adaptation to CAVB and might contribute to arrhythmogenesis.
Methods and Results—In enzymatically isolated myocytes, cell shortening, Ca2+ release from the sarcoplasmic reticulum (SR), and SR Ca2+ content were enhanced at low stimulation frequencies. Ca2+ influx through L-type Ca2+ channels was unchanged, but Ca2+ influx via the Na/Ca exchanger was increased and contributed to Ca2+ loading of the SR. Inward Na/Ca exchange currents were also larger. Changes in Ca2+ fluxes were less pronounced in the right versus left ventricle.
Conclusions—Enhanced Na/Ca exchange activity may improve contractile adaptation to CAVB but at the same time facilitate arrhythmias by (1) increasing the propensity to Ca2+ overload, (2) providing more inward current leading to (nonhomogeneous) action potential prolongation, and (3) enhancing (arrhythmogenic) currents during spontaneous Ca2+ release.
Key Words: calcium • myocytes • sarcoplasmic reticulum • hypertrophy
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