Markovian Models of Low and High Activity Levals of Cardiac Ryanodine Receptors (H2 Model)

Model Status

This CellML model represents the 'H2' Markovian model of the RyR channel activity. The model runs in both OpenCell and COR and the units are consistent. Unfortunately, there are no comparable figures in the published paper for a curation check of the CellML model results.

Model Structure

ABSTRACT: The modal gating behavior of single sheep cardiac sarcoplasmic reticulum (SR) Ca2+-release/ryanodine receptor (RyR) channels was assessed. We find that the gating of RyR channels spontaneously shifts between high (H) and low (L) levels of activity and inactive periods where no channel openings are detected (I). Moreover, we find that there is evidence for multiple gating modes within H activity, which we term H1 and H2 mode. Our results demonstrate that the underlying mechanisms regulating gating are similar in native and purified channels. Dwell-time distributions of L activity were best fitted by three open and five closed significant exponential components whereas dwell-time distributions of H1 activity were best fitted by two to three open and four closed significant exponential components. Increases in cytosolic [Ca2+] cause an increase in open probability (Po) within L activity and an increase in the probability of occurrence of H activity. Open lifetime distributions within L activity were Ca2+ independent whereas open lifetime distributions within H activity were Ca2+ dependent. This study is the first attempt to estimate RyR single-channel kinetic parameters from sequences of idealized dwell-times and to develop kinetic models of RyR gating using the criterion of maximum likelihood. We propose distinct kinetic schemes for L, H1, and H2 activity that describe the major features of sheep cardiac RyR channel gating at these levels of activity.

The original paper reference is cited below:

Markovian Models Of Low And High Activity Levels Of Cardiac Ryanodine Receptors, Elena Saftenku, Alan J. Williams and Rebecca Sitsapesan, 2001, Biophysical Journal, 80, 2727-2741. PubMed ID: 11371448

Kinetic models of the gating of cardiac ryanodine receptors at low and high levels of activity.