© 1999 American Heart Association, Inc.
Original Contribution |
The Sarcoplasmic Reticulum and the Na+/Ca2+ Exchanger Both Contribute to the Ca2+ Transient of Failing Human Ventricular Myocytes
From the Temple University School of Medicine Departments of Physiology (K.D., J.A.M., S.R.H.), Internal Medicine (K.B.M.), and Surgery (V.J.), Philadelphia, Pa.
Correspondence to Steven R. Houser, PhD, Professor of Physiology, Temple University School of Medicine Department of Physiology, 3420 N Broad St, Philadelphia, PA 19140. E-mail srhouser{at}astro.ocis.temple.edu
Abstract—Our objective was to determine the respective roles of the sarcoplasmic reticulum (SR) and the Na+/Ca2+ exchanger in the small, slowly decaying Ca2+ transients of failing human ventricular myocytes. Left ventricular myocytes were isolated from explanted hearts of patients with severe heart failure (n=18). Cytosolic Ca2+, contraction, and action potentials were measured by using indo-1, edge detection, and patch pipettes, respectively. Selective inhibitors of SR Ca2+ transport (thapsigargin) and reverse-mode Na+/Ca2+ exchange activity (No. 7943, Kanebo Ltd) were used to define the respective contribution of these processes to the Ca2+ transient. Ca2+ transients and contractions induced by action potentials (AP transients) at 0.5 Hz exhibited phasic and tonic components. The duration of the tonic component was determined by the action potential duration. Ca2+ transients induced by caffeine (Caf transients) exhibited only a phasic component with a rapid rate of decay that was dependent on extracellular Na+. The SR Ca2+-ATPase inhibitor thapsigargin abolished the phasic component of the AP Ca2+ transient and of the Caf transient but had no significant effect on the tonic component of the AP transient. The Na+/Ca2+ exchange inhibitor No. 7943 eliminated the tonic component of the AP transient and reduced the magnitude of the phasic component. In failing human myocytes, Ca2+ transients and contractions exhibit an SR-related, phasic component and a slow, reverse-mode Na+/Ca2+ exchange–related tonic component. These findings suggest that Ca2+ influx via reverse-mode Na+/Ca2+ exchange during the action potential may contribute to the slow decay of the Ca2+ transient in failing human myocytes.
Key Words: calcium transient • isolated myocyte • heart failure • Na+/Ca2+ exchanger • sarcoplasmic reticulum
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