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 human atria. Fluorescence measurements using fura‐2 were carried out in conjunction 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 rapid application of caffeine or by Ca2+ current elicited inward Na(+)‐Ca2+ exchange currents (INa‐Ca). The magnitude of INa‐Ca was largest in hamster, smallest in rat, with guinea‐pig and human myocytes having intermediate values. The ratio of caffeine‐induced exchanger current densities, normalized with respect to the peak Ca2+ release, was 4:2:1.5:1 for hamster > guinea‐pig > or = human > or = rat myocytes. 3. The rates of Ca2+ removal in the presence of caffeine, which reflect primarily the Ca2+ extruding activity of the Na(+)‐Ca2+ exchanger, followed the same order of hamster > guinea‐pig > or = human > or = rat. 4. The kinetics of INa‐Ca vs. Ca2+ transients were different among species. In rat myocytes, the kinetics of the INa‐Ca and the Ca2+ transients were similar, with INa‐Ca linearly proportional to intracellular Ca2+ concentration ([Ca2+]i). In hamster myocytes, the time course of INa‐Ca tracked only the declining phase of the Ca2+ transient with INa‐Ca having faster kinetics during the Ca2+ release. These findings suggest that the Ca2+ concentrations in the vicinity of the exchanger were significantly higher than those of the cytosol during Ca2+ release in hamster myocytes. 5. We concluded that there are significant species differences in the exchanger activity of cardiac myocytes, arising from differences in exchanger densities, their modulation and/or their spatial distribution with respect to the ryanodine receptors of cardiac myocytes.