Intracellular [Ca²⁺] related to rate of force development in twitch contraction of heart

The relation between the rate of rise of tension (dF/dt) and intracellular free Ca²⁺ concentration ([Ca²⁺](i)) during twitch contraction was investigated in mammalian ventricular myocardium. [Ca²⁺](i) was assessed from luminescence emitted by ferret papillary muscles microinjected with the calcium-regulated photoprotein aequorin. Evidence was found that during the phase of rising tension following maximum positive dF/dt, there was an approximately linear relationship between dF/dt at a given instant and the estimated [Ca²⁺](i) at that same instant. A single such instantaneous relationship held true for physiological contractions of widely varying strength (n = 5 preparations), up to 65.3 ± 6.0% (means ± SE) of maximal Ca²⁺-activated force, as assessed from maximally activated cardiac tetani. Furthermore, the identical relationship determined from physiological contractions also held true for virtually the entire rising phase of tension in contractions with [Ca²⁺](i) transients slowed (~4- to 5-fold) by exposure of muscles to 5 μM ryanodine (n = 5 preparations). That a unique relation applies to contractions of both vastly different strength and time course provides evidence that the correlation between instantaneous dF/dt and [Ca²⁺](i) is not merely fortuitous but indicates a fundamental property of myocardium. Such a property provides considerable insight into many features of physiological contraction and may represent a central clue as to the mechanism of activation in mammalian cardiac muscles.