Model discrimination for Ca2+ -dependent regulation of myosin light chain kinase in smooth muscle contraction

FEBS Lett. 2018 Aug;592(16):2811-2821. doi: 10.1002/1873-3468.13207. Epub 2018 Aug 13.

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.

Keywords: calcium signaling; calmodulin; excitation-contraction coupling; linear framework; mathematical modeling; myosin light chain kinase.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calmodulin / metabolism*
  • Humans
  • Models, Molecular
  • Models, Theoretical
  • Muscle Contraction*
  • Muscle, Smooth / physiology
  • Myosin-Light-Chain Kinase / chemistry
  • Myosin-Light-Chain Kinase / metabolism*

Substances

  • Calmodulin
  • Myosin-Light-Chain Kinase
  • Calcium