Markovian Models of Low and High Activity Levals of Cardiac Ryanodine Receptors

Model Status

This model has been recoded to remove the reaction elements by Catherine Lloyd. This file represents the 'low' Markovian model of the RyR channel activity. This file is known to load and run in PCEnv, but the output of the model may not be correct. Unfortunately, there is not enough information in the original paper to fully replicate this model.

Model Structure

In cardiac cells, Ca²⁺ influx through L-type Ca²⁺-channels triggers the opening of ryanodine receptor (RyR) channels, thereby releasing Ca²⁺ from the sarcoplasmic reticulum (SR) causing muscle contraction. The mechanisms underlying Ca²⁺ activation and inactivation of RyR channels have been extensively studied. In their 2001 paper, Elena Saftenku, Alan J. Williams and Rebecca Sitsapesan found that the gating of RyR channels spontaneously shifts between high (H) and low (L) levels of activity and that there is evidence for multiple gating modes within H activity (H1 and H2). They propose distinct kinetic schemes for L, H1, and H2 activity that describe the major features of cardiac RyR channel gating (see the figure below).

The complete 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. (Full text and PDF versions of the article are available to subscribers on the Biophysical Journal website.) PubMed ID: 11371448

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