Competition and redistribution among calcium transport systems in rabbit cardiac myocytes

Normally the sarcoplasmic reticular calcium pump and sarcolemmal Na/Ca exchange compete and are the primary mechanisms responsible for reducing [Ca]i during cardiac relaxation. The sarcolemmal calcium pump and mitochondrial calcium uptake are much slower, but may also participate in [Ca]i regulation. The aim of this study was to provide a clearer understanding of the interaction of these mechanisms. Myocyte shortening and [Ca]i transients (using indo-1 fluorescence) were measured in rabbit ventricular myocytes, with similar results. The t1/2 of twitch relaxation was 0.17(SEM 0.03) s. Contractures induced by 10 mM caffeine (caffeine contraction) relaxed more slowly [t1/2 = 0.54(0.07) s] due to prevention of sarcoplasmic reticular calcium uptake. When the Na/Ca exchange was also blocked by perfusion with 0Na,0Ca solution, the peak of the caffeine contraction was increased (by 44%) and relaxation was slowed about 16-fold [t1/2 = 8.8(0.8) s]. Blocking mitochondrial calcium uptake by including 1 microM FCCP + 1 microM oligomycin in the 0Na,0Ca solution slowed the relaxation of the caffeine contraction further [t1/2 = 19.7(3.2) s]. Inhibition of the sarcolemmal calcium pump by perfusion with 0Na, 10 mM Ca during caffeine contraction also increased the relaxation t1/2 to 27.5(6.9) s. Inhibition of all four calcium transport systems almost abolished relaxation. It is also shown that calcium which was taken up by the mitochondria during relaxation of the caffeine contraction in 0Na,0Ca gradually redistributed (with tau = 41 s) back to the sarcoplasmic reticulum after caffeine was removed. A second caffeine contraction could then be elicited.(ABSTRACT TRUNCATED AT 250 WORDS)