Model-based analysis of elementary Ca(2+) release events in skinned mammalian skeletal muscle fibres

Eur Biophys J. 2002 Sep;31(5):331-40. doi: 10.1007/s00249-002-0223-5. Epub 2002 Jun 11.

Abstract

Using high temporally and spatially resolved confocal laser scanning microscopy, we have recently demonstrated the existence of elementary Ca(2+) release events (ECRE) in chemically and mechanically skinned fibres from adult mammalian skeletal muscle. Here, we present a first approach to the analysis of mammalian ECRE with a spatio-temporal mathematical model of Ca(2+) ion distribution in skinned muscle fibre preparations. The differential equations for the main processes, including sarcoplasmic reticulum Ca(2+) handling, are solved in a 2-D cylindrical geometry by the method of explicit finite differences. By calculating the various spatio-temporal ion concentrations as well as the theoretical fluorescence signals for confocal microscopy, corrected for the point spread function, the model output can be directly correlated with the experimental data. Thus, the basic features of mammalian ECRE were successfully reproduced with our model. In particular, under our model assumptions a considerable depletion of luminal free calcium is predicted even for short spark-like ECRE. For a full understanding of the molecular and sub-cellular events responsible for EC coupling it is vitally important to combine the experimental and modelling approaches to elucidate the contribution of mammalian ECRE to the global Ca(2+) release and its alteration under various physiological and also pathophysiological conditions.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cell Membrane / metabolism*
  • Computer Simulation*
  • Diffusion
  • Foot / physiology
  • In Vitro Techniques
  • Male
  • Membrane Potentials / physiology
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Confocal
  • Models, Biological*
  • Muscle Fibers, Fast-Twitch / cytology
  • Muscle Fibers, Fast-Twitch / metabolism*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism
  • Reproducibility of Results
  • Sarcoplasmic Reticulum / metabolism*
  • Sensitivity and Specificity

Substances

  • Calcium