RELAXATION IN RABBIT AND RAT CARDIAC-CELLS - SPECIES-DEPENDENT DIFFERENCES IN CELLULAR MECHANISMS

The roles of the sarcoplasmic reticulum (SR) Ca2+-ATPase and Na+-Ca2exchange in Ca2+ removal from cytosol were compared in isolated rabbit and rat ventricular myocytes during caffeine contractures and electri cally stimulated twitches. Cell shortening and intracellular calcium c oncentration ([Ca2+](i)) were measured in indo-1-loaded cells. 2. Na+- Ca2+ exchange was inhibited by replacement of external Na+ by Li+. To avoid net changes in cell or SR Ca2+ load during a twitch in 0 Na+ sol ution, intracellular Na+ (Na-1(+)) was depleted using a long pre-perfu sion with 0Na(+), 0Ca(2+) solution. SR Ca2+ accumulation was inhibited by caffeine or thapsigargin (TG). 3. Relaxation of steady-state twitc hes was 2-fold faster in rat than in rabbit (before and after Na-1(+) depletion). In contrast, caffeine contractures (where SR Ca2+ accumula tion is inhibited), relaxed faster in rabbit cells. Removal of externa l Naf increased the half-time for relaxation of caffeine contractures 15- and 5-fold in rabbit and rat myocytes respectively (and increased contracture amplitude in rabbit cells only). The time course of relaxa tion in 0 Na+, 0 Ca2+ solution was similar in the two species. 4. Inhi bition of the Na+-Ca-2 exchange during a twitch increased the [Ca2+](i ) transient amplitude (Delta[Ca2+](i)) by 50 % and the time constant o f [Ca2+](i) decline (tau) by 45% in rabbit myocytes. A smaller increas e in tau (20%) and no change in Delta[Ca2+](i) were observed in rat ce lls in 0 Na+ solution. [Ca2+](i) transients remained more rapid in rat cells. 5. Inhibition of the SR Ca2+-ATPase during a twitch enhanced D elta[Ca2+](i) by 25% in both species. The increase in tau after TG exp osure was greater in rat (9-fold) than in rabbit myocytes (2-fold), wh ich caused [Ca2+](i) decline to be 70% slower in rat compared with rab bit cells. The time course of [Ca2+](i) decline during twitch in TG-tr eated cells was similar to that during caffeine application in control cells. 6. Combined inhibition of these Ca2+ transport systems markedl y slowed the time course of [Ca2+](i) decline, so that tau was virtual ly the same in both species and comparable to that during caffeine app lication in 0 Na+, 0 Ca2+ solution. Thus, the combined participation o f slow Ca2+ transport mechanisms (mitochondrial Ca2+ uptake and sarcol emmal Ca2+- ATPase) is similar in these species.7. We conclude that du ring the decline of the [Ca2+](i) transient, the Na+-Ca2+ exchange is about 2- to S-fold faster in rabbit than in rat, whereas the XR Ca2+-A TPase is 2- to 3-fold faster in the rat. While the SR Ca2+-ATPase is m ore powerful than the Na+-Ca2+ exchange in both cell types the dominan ce is much more marked in rat(similar to 13-fold vs. 2.5-fold in rabbi t). Finally we estimate that the fraction of Ca2+ transported by the S R, Na+-Ca2+ exchange and slow systems during a twitch are 70, 28 and 2 % respectively in rabbit myocytes and 92, 7 and 1% respectively in rat myocytes.