期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 322, 期 5, 页码 1065-1088出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/S0022-2836(02)00855-0
关键词
model; cooperativity; ADP; P-i; S1
资金
- NHLBI NIH HHS [HL-52508] Funding Source: Medline
- PHS HHS [R-90406] Funding Source: Medline
We have formulated a three-compartment model of muscle activation that includes both strong cross-bridge (XB) and Ca2+-activatecl regulatory-unit (RU) mediated nearest-neighbor cooperative influences. The model is based on the tight coupling premise-that XB retain activating Ca2+ on the thin filament. Using global non-linear least-squares, the model produced excellent fits to experimental steady-state force-pCa and ATPase-pCa data from skinned rat soleus fibers. In terms of the model, nearest-neighbor influences over the range of Ca2+ required for activation cause the Ca2+ dissociation rate from regulatory-units (k(off)) to decrease and the cross-bridge association rate (f) to increase each 2 more than tenfold. Moreover, the rate variations occur in separate Ca2+ regimes. The energy of activation governing f is strongly influenced by both neighboring RU and XB. In contrast, the energy of activation governing k(off) is less affected by neighboring XB than by neighboring RU. Nearest-neighbor cooperative influences provide both an overall sensitization to Ca2+ and the well-known steep response of force to free Ca2+. The apparent sensitivity for Ca2+-activation of force and ATPase is a function of cross-bridge kinetic rates. The model and derived parameter set produce simulated behavior in qualitative agreement with steady-state experiments reported in the literature for partial TnC replacement, increased [P-i], increased [ADP], and MalNEt-S1 addition. The model is an initial attempt to construct a general theory of striated muscle activation-one that can be consistently used to interpret data from various types of muscle manipulation experiments. (C) 2002 Elsevier Science Ltd. All rights reserved.
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