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.
Sham
J S
JS
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA.
Hatem
S N
SN
Morad
M
M
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000502:physiology*; D002648:Child; D006224:Cricetinae; D004594:Electrophysiology; D006168:Guinea Pigs; D006325:Heart Atria / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D007700:Kinetics; D008297:Male; D008322:Mammals; D008564:Membrane Potentials / Q000502:physiology; D008647:Mesocricetus; D009206:Myocardium / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger
D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D002110:Caffeine; D012964:Sodium; D002118:Calcium