SPECIES-DIFFERENCES IN THE ACTIVITY OF THE NA-CA2+ EXCHANGER IN MAMMALIAN CARDIAC MYOCYTES()

1. Species differences in the activity of the exchanger were evaluated in isolated myocytes from rat, guinea-pig, hamster ventricles and hum an atria. Fluorescence measurements using fura-2 were carried out in c onjunction with the whole-cell patch-clamp technique for simultaneous recording of membrane currents and intracellular Ca2+ concentration. 2 . Ca2+ release from sarcoplasmic reticulum (SR) induced either by rapi d application of caffeine or by Ca2+ current elicited inward Na+-Ca2exchange currents (I-Na-Ca). The magnitude of I-Na-Ca was largest in h amster, smallest in rat, with guinea-pig and human myocytes having int ermediate values. The ratio of caffeine-induced exchanger current dens ities, normalized with respect to the peak Ca2+ release, was 4:2:1.5:1 for hamster > guinea-pig greater than or equal to human greater than or equal to rat myocytes. 3. The rates of Ca2+ removal in the presence of caffeine, which reflect primarily the Ca2+ extruding activity of t he Na+-Ca2+ exchanger, followed the same order of hamster > guinea-pig greater than or equal to human greater than or equal to rat. 4. The k inetics of I-Na-Ca vs. Ca2+ transients sr ere different among species. In rat myocytes, the kinetics of the I-Na-Ca and the Ca2+ transients mere similar, with I-Na-Ca linearly proportional to intracellular Ca2 concentration ([Ca2+](i)). In hamster myocytes, the time course of I- Na-Ca tracked only the declining phase of the Ca2+ transient with I-Na -Ca having faster kinetics during the Ca2+ release. These findings sug gest that the Ca2+ concentrations in the vicinity of the exchanger wer e significantly higher than those of the cytosol during Ca2+ release i n hamster myocytes. 5. We concluded that there are significant species differences in the exchanger activity of cardiac myocytes, arising fr om differences in exchanger densities, their modulation and/or their s patial distribution with respect to the ryanodine receptors of cardiac myocytes.