1. Model discrimination for Ca 2+ ‐dependent regulation of myosin light chain kinase in smooth muscle contraction
- Author
-
John W. Biddle, Joseph P. Dexter, and Jeremy Gunawardena
- Subjects
0301 basic medicine ,Physics ,Steady state (electronics) ,Myosin light-chain kinase ,Calmodulin ,biology ,Computer simulation ,Mathematical model ,Differential equation ,Biophysics ,Cell Biology ,Smooth muscle contraction ,Biochemistry ,Quantitative Biology::Subcellular Processes ,Coupling (electronics) ,03 medical and health sciences ,030104 developmental biology ,Structural Biology ,Genetics ,biology.protein ,Biological system ,Molecular Biology - Abstract
Excitation-contraction coupling in smooth muscle is mediated by the Ca2+ - and calmodulin-dependent regulation of myosin light chain kinase. The precise mechanism of this regulation remains controversial, and several mathematical models have been proposed for the interaction of the three species. These models have previously been analyzed at steady state primarily by numerical simulation of differential equations, for which parameter values must be estimated from data. Here, we use the linear framework for timescale separation to demonstrate that models of this general kind can be solved analytically for an equilibrium steady state, without having to determine parameter values. This analysis leads to parameter-independent methods for discriminating between the models, for which we propose experiments that could be performed with existing methods.
- Published
- 2018