Intracellular calcium related to force development in twitch contraction of mammalian myocardium

To characterize the relationship between force production and Ca2+ occupancy of troponin C, investigators have related peak intracellular Ca2+, measured with a variety of Ca2(+)-indicators, and peak force during twitches. Inherent in the force-Ca2+ relationship is the responsiveness of the myofilaments to Ca2+ which can be altered by different pharmacological manipulations. In this study we compared the force-Ca2+ relationship obtained in aequorin-injected papillary muscles and saponin skinned trabeculae from control, right ventricular pressure-overload hypertrophy (POH), and hyperthyroid ferret hearts. In POH, the twitch and Ca2+i transient were prolonged as compared to control. Force-Ca2+ relationships from skinned fiber preparations were superimposable between control and POH. The peak force-peak Ca2+i relationship in intact muscles from POH was shifted to the left as compared to control. In hyperthyroid hearts, the twitch and Ca2+i were abbreviated. Force-Ca2+i relationships from skinned fiber preparations were superimposable between control and thyrotoxic hearts. The peak force-peak Ca2+i relationship in intact muscles from hyperthyroid hearts was shifted to the right as compared to control. Our findings indicate that time course changes in the calcium transient artifacturally shift the peak force-peak calcium relationship in a predictable manner. Therefore, this relationship can not be used to address changes at the level of the myofilaments as previously suggested.