Differences in Ca²⁺-handling and sarcoplasmic reticulum Ca²⁺-content in isolated rat and rabbit myocardium

We made novel measurements of the influence of rest intervals and stimulation frequency on twitch contractions and on sarcoplasmic reticulum (SR) Ca^2--content (using rapid cooling contractures, RCCs) in isolated ventricular muscle strips from rat and rabbit hearts at a physiological temperature of 37 °C. In addition, the frequency-dependent relative contribution of SR Ca²⁺-uptake and Na⁺/Ca²⁺-exchange for cytosolic Ca²⁺-removal was assessed by paired RCCs. With increasing rest intervals (1-240 s) post-rest twitch force and RCC amplitude decreased monotonically in rabbit myocardium (after 240 s by 45 ± 10% and 61 ± 11%, respectively: P<0.05, n = 14). In contrast, rat myocardium (n = 11) exhibited a parallel increase in post-rest twitch force (by 67 ± 16% at 240 s; P<0.05) and RCC amplitude (by 20 ± 14%: P<0.05). In rabbit myocardium (n=11), increasing stimulation frequency from 0.25 to 3 Hz increased twitch force by 295 ± 50% (P<0.05) and RCC amplitude by 305 ± 80% (P<0.05). In contrast, in rat myocardium (n = 6), twitch force declined by 43 ± 7% (P<0.05), while RCC amplitude decreased only insignificantly (by 16 ± 7%). The SR Ca²⁺-uptake relative to Na⁺/Ca²⁺-exchange (based on paired RCCs) increased progressively with frequency in rabbit, but not in rat myocardium (∼66 ± 2% at all frequencies). We conclude that increased SR Ca²⁺-load contributes to the positive force-frequency relationship in rabbits and post-rest potentiation of twitch force in rats. Decreased SR Ca²⁺-load contributes to post-rest decay of twitch force in rabbits, but may play only a minor role in the negative force-frequency relationship in rats. SR Ca²⁺-release channel refractoriness may contribute importantly to the negative force-frequency relationship in rat and recovery from refractoriness may contribute to post-rest potentiation.