Ca2+ Sensitivity of Contractile Machinery and Ca2+ Handling Energy. Simulation.:Simulation

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Myocardial Ca2+ handling during excitation-contraction coupling has been modelled mathematically to gain a better insight into the expectation that Ca2+ sensitization of contractile machinery may save myocardial energy utiliza-tion for Ca2+ handling. The basic model of myocardial Ca2+ kinetics and mechanoenergetics involved the sarcoplasmic reticulum (SR), sarcoplasm, tro-ponin C (Tn) and crossbridges (CB). The relations among the released Ca2+ ions from the SR, peak concentrations of sarcoplasmic free Ca2+ ([Ca2+]i) and Ca2+-bound troponin ([TnCa]) and peak contractile force were computed, based upon the assumptions that the released Ca2+ ions diffuse as free Ca2+ in sarcoplasm, bind kinetically with Tn with an association rate constant of k1, dissociate from TnCa with a dissociation rate constant of k2, and are seques-tered into the SR with consumption of ATP. TnCa was associated with GB cycling to develop force with a set of given on and off rate constants. The association constant Ka (=k1/k2) of TnCa as an index of Ca2+ sensitivity of Tn was varied 32-fold from 0.25 to 8/μM. Results showed that Ca2+ sensitization from a lower Ka level could most sharply decrease the total Ca2+ release re-quired to develop the same contractile force. Thus, it would reduce the total Ca2+ handling energy that the SR uses to maintain the same contractility.
International Heart Journal刊行会の論文