How does the ryanodine receptor in the ventricular myocyte wake up: by a single or by multiple open L-type Ca2+ channels?

Eur Biophys J. 2012 Jan;41(1):27-39. doi: 10.1007/s00249-011-0755-7. Epub 2011 Oct 1.

Abstract

We study here the early stage of Ca(2+)-induced Ca(2+) release (CICR) in the diadic cleft of cardiac ventricular myocytes. A crucial question for this mechanism is whether the activation of the ryanodine receptors (RyRs) is triggered by one or by multiple open L-type Ca(2+) channels (LCCs). We address the problem through a modelling approach that allows us to investigate both possibilities. The model is based on a spatially resolved description of a Ca(2+) release unit (CaRU), consisting of the junctional sarcoplasmic reticulum and the diadic cleft, with well-defined channel placement. By taking advantage of largely varying time scales of the Ca(2+) dynamics in the diadic cleft, the governing equations can be reduced to one ordinary differential equation that describes the Ca(2+) fluxes, the electric field due to surface charges and diffusion. Our study shows that the mechanisms of the early stage of CICR shape measurable properties of CICR in a characteristic way. From here we conclude that the activation of RyRs requires multiple open LCCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Calcium Channels, L-Type / metabolism*
  • Electricity
  • Heart Ventricles / cytology*
  • Ion Channel Gating*
  • Membrane Potentials
  • Models, Biological*
  • Muscle Cells / cytology
  • Muscle Cells / metabolism*
  • Ryanodine Receptor Calcium Release Channel / metabolism*
  • Sarcoplasmic Reticulum / metabolism
  • Stochastic Processes

Substances

  • Calcium Channels, L-Type
  • Ryanodine Receptor Calcium Release Channel
  • Calcium