Abstract
We have formulated a three-compartment model of muscle activation that includes both strong cross-bridge (XB) and Ca2+-activated 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 (koff) to decrease and the cross-bridge association rate (f) to increase each 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 koff 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 [Pi], 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1065-1088 |
| Number of pages | 24 |
| Journal | Journal of Molecular Biology |
| Volume | 322 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 14 2002 |
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Keywords
- ADP
- Cooperativity
- Model
- P
- S1
ASJC Scopus subject areas
- Virology
Cite this
Activation of striated muscle : Nearest-neighbor regulatory-unit and cross-bridge influence on myofilament kinetics. / Robinson, John M.; Wang, Ying; Kerrick, W. Glenn; Kawai, Ryoichi; Cheung, Herbert C.
In: Journal of Molecular Biology, Vol. 322, No. 5, 14.11.2002, p. 1065-1088.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Activation of striated muscle
T2 - Nearest-neighbor regulatory-unit and cross-bridge influence on myofilament kinetics
AU - Robinson, John M.
AU - Wang, Ying
AU - Kerrick, W. Glenn
AU - Kawai, Ryoichi
AU - Cheung, Herbert C.
PY - 2002/11/14
Y1 - 2002/11/14
N2 - We have formulated a three-compartment model of muscle activation that includes both strong cross-bridge (XB) and Ca2+-activated 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 (koff) to decrease and the cross-bridge association rate (f) to increase each 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 koff 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 [Pi], 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.
AB - We have formulated a three-compartment model of muscle activation that includes both strong cross-bridge (XB) and Ca2+-activated 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 (koff) to decrease and the cross-bridge association rate (f) to increase each 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 koff 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 [Pi], 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.
KW - ADP
KW - Cooperativity
KW - Model
KW - P
KW - S1
UR - http://www.scopus.com/inward/record.url?scp=0036409388&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036409388&partnerID=8YFLogxK
U2 - 10.1016/S0022-2836(02)00855-0
DO - 10.1016/S0022-2836(02)00855-0
M3 - Article
VL - 322
SP - 1065
EP - 1088
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 5
ER -