Modelling calcium microdomains using homogenisation

Erin R. Higgins, Pranay Goel, Jose L. Puglisi, Donald M Bers, Mark Cannell, James Sneyd

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Microdomains of calcium (i.e., areas on the nanometer scale that have qualitatively different calcium concentrations from that in the bulk cytosol) are known to be important in many situations. In cardiac cells, for instance, a calcium microdomain between the L-type channels and the ryanodine receptors, the so-called diadic cleft, is where the majority of the control of calcium release occurs. In other cell types that exhibit calcium oscillations and waves, the importance of microdomains in the vicinity of clusters of inositol trisphosphate receptors, or between the endoplasmic reticulum (ER) and other internal organelles or the plasma membrane, is clear. Given the limits of computational power, it is not currently realistic to model an entire cellular cytoplasm by incorporating detailed structural information about the ER throughout the entire cytoplasm. Hence, most models use a homogenised approach, assuming that both cytoplasm and ER coexist at each point of the domain. Conversely, microdomain models can be constructed, in which detailed structural information can be incorporated, but, until now, methods have not been developed for linking such a microdomain model to a model at the level of the entire cell. Using the homogenisation approach we developed in an earlier paper [Goel, P., Friedman, A., Sneyd, J., 2006. Homogenization of the cell cytoplasm: the calcium bidomain equations. SIAM J. Multiscale Modeling Simulation, in press] we show how a multiscale model of a calcium microdomain can be constructed. In this model a detailed model of the microdomain (in which the ER and the cytoplasm are separate compartments) is coupled to a homogenised model of the entire cell in a rigorous way. Our method is illustrated by a simple model of the diadic cleft of a cardiac half-sarcomere.

Original languageEnglish (US)
Pages (from-to)623-644
Number of pages22
JournalJournal of Theoretical Biology
Volume247
Issue number4
DOIs
StatePublished - Aug 21 2007
Externally publishedYes

    Fingerprint

Keywords

  • Calcium microdomains
  • Calcium oscillations
  • Effective diffusion coefficients
  • Excitation-contraction coupling
  • Homogenisation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Higgins, E. R., Goel, P., Puglisi, J. L., Bers, D. M., Cannell, M., & Sneyd, J. (2007). Modelling calcium microdomains using homogenisation. Journal of Theoretical Biology, 247(4), 623-644. https://doi.org/10.1016/j.jtbi.2007.03.019