Ca2+ sensitivity of contractile machinery and Ca2+ handling energy. Simulation.
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 utilization for Ca2+ handling. The basic model of myocardial Ca2+ kinetics and mechanoenergetics involved the sarcoplasmic reticulum (SR), sarcoplasm, troponin C (Tn) and crossbridges (CB). The relations among the released Ca2+ ions from the SR, peak concentrations of sarcoplasmic free Ca2+ ([Ca2+]i) and Ca(2+)-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 sequestered into the SR with consumption of ATP. TnCa was associated with CB 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/microM. Results showed that Ca2+ sensitization from a lower Ka level could most sharply decrease the total Ca2+ release required to develop the same contractile force. Thus, it would reduce the total Ca2+ handling energy that the SR uses to maintain the same contractility.
Namba
T
T
Second Department of Physiology, Okayama University Medical School, Japan.
Takaki
M
M
Araki
J
J
Ishioka
K
K
Akashi
T
T
Zhao
L Y
LY
Matsushita
T
T
Ito
H
H
Fujii
W
W
Matsubara
H
H
D002118:Calcium / Q000502:physiology*; D003198:Computer Simulation; D004734:Energy Metabolism; D006801:Humans; D008955:Models, Cardiovascular; D008962:Models, Theoretical; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014336:Troponin / Q000378:metabolism; D019209:Troponin C
D014336:Troponin; D019209:Troponin C; D002118:Calcium