title: How does the ryanodine receptor in the ventricular myocyte wake up: by a single or by multiple open L-type Ca2+ channels?
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.
authors.affiliation: Max Delbrück Center of Moleculare Medicine, Robert-Rössle-Strasse 10, Berlin, Germany. thomas.schendel@mdc-berlin.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Schendel
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Thul
authors.forename: James
authors.initials: J
authors.lastname: Sneyd
authors.forename: Martin
authors.initials: M
authors.lastname: Falcke
mesh_terms: D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D004560:Electricity; D006352:Heart Ventricles / Q000166:cytology*; D015640:Ion Channel Gating; D008564:Membrane Potentials; D008954:Models, Biological; D032342:Muscle Cells / Q000166:cytology / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013269:Stochastic Processes
chemical_list: D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium