THE RELATIONSHIP BETWEEN CONTRACTILE-FORCE AND INTRACELLULAR [CA2+] IN INTACT RAT CARDIAC TRABECULAE

The control of force by [Ca2+] was investigated in rat cardiac trabecu lae loaded with fura-2 salt. At sarcomere lengths of 2.1-2.3 mu m, the steady state force-[Ca2+](i) relationship during tetanization in the presence of ryanodine was half maximally activated at a [Ca2+](i) of 0 .65 +/- 0.19 mu M with a Hill coefficient of 5.2 +/- 1.2 (mean +/- SD, n = 9), and the maximal stress produced at saturating [Ca2+](i) equal led 121 +/- 35 mN/mm(2) (n = 9). The dependence of steady state force on [Ca2+](i) was identical in muscles tetanized in the presence of the Ca2+-ATPase inhibitor cyclopiazonic acid (CPA). The force-[Ca2+](i) r elationship during the relaxation of twitches in the presence of CPA c oincided exactly to that measured at steady state during tetani, sugge sting that CPA slows the decay rate of [Ca2+](i) sufficiently to allow the force to come into a steady state with the [Ca2+](i). In contrast , the relationship of force to [Ca2+](i) during the relaxation phase o f control twitches was shifted leftward relative to the steady state r elationship, establishing that relaxation is limited by the contractil e system itself, not by Ca2+ removal from the cytosol. Under control c onditions the force-[Ca2+](i) relationship, quantified at the time of peak twitch force (i.e., dF/dt = 0), coincided fairly well with steady state measurements in some trabeculae (i.e., three of seven). However , the force-[Ca2+](i) relationship at peak force did not correspond to the steady state measurements after the application of 5 mM 2,3-butan edione monoxime (BDM) (to accelerate cross-bridge kinetics) or 100 mu M CPA (to slow the relaxation of the [Ca2+](i) transient). Therefore, we conclude that the relationship of force to [Ca2+](i) during physiol ogical twitch contractions cannot be used to predict the steady state relationship.