Restitution of contractility in single ventricular myocytes of guinea pig heart

Objective: Our aim was to assess the extent to which changes in intracellular Ca2+ stores contribute to mechanical restitution in heart muscle. Methods: Single, isolated guinea pig ventricular cells were voltage clamped at -45 mV and stimulated continuously at 0.5 or 2 Hz with 200 ms depolarizing pulses (35 degrees C). The recoveries of the peak of contraction force (F-p) and the calcium current (I-Ca) between beats were measured in contractions interpolated at various intervals (t(d)) after a conditioning twitch. Recovery of SR Ca2+ load was inferred from the peak magnitude (C-p) of similarly interpolated contractures, induced by rapid application of 5 mM caffeine. Results: For a conditioning stimulus rate of 0.5 Hz, both F-p and I-Ca were very small for small t(d) and recovered along similar time courses with a t(1/2) of about 50 ms. C-p was maximal at as early a time after a previous contraction as could be measured, at which time F-p was 56% of maximal. C-p declined throughout the stimulus interval to about 50% of its maximal value. Similar results were obtained for a conditioning stimulus rate of 2 Hz, at which rate both F-p and C-p were increased by a factor of 2. Conclusions: The time course of mechanical restitution is coincident with the recovery of I-Ca from inactivation. Caffeine-releasable intracellular calcium stores are fully recovered soon after a contraction and well before mechanical restitution is complete.