Markovian Models of Low and High Activity Levels of Cardiac Ryanodine Receptors
Catherine
Lloyd
Bioengineering Institute, University of Auckland
Model Status
This CellML model represents the 'low' 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
Schematic diagrams of the RyR models
Kinetic models of the gating of cardiac ryanodine receptors at low and high levels of activity.
$\frac{d \mathrm{C1}}{d \mathrm{time}}=\mathrm{C2C1}\mathrm{C2}-\mathrm{C1C2}\mathrm{Ca}\mathrm{C2}$
$\frac{d \mathrm{C2}}{d \mathrm{time}}=\mathrm{C1C2}\mathrm{Ca}\mathrm{C1}+\mathrm{C3C2}\mathrm{C3}+\mathrm{C5C2}\mathrm{C5}-\mathrm{C2C1}\mathrm{C2}+\mathrm{C2C3}\mathrm{Ca}\mathrm{C2}+\mathrm{C2C5}\mathrm{C2}$
$\frac{d \mathrm{C3}}{d \mathrm{time}}=\mathrm{C2C3}\mathrm{Ca}\mathrm{C2}+\mathrm{O1C3}\mathrm{O1}+\mathrm{O3C3}\mathrm{O3}+\mathrm{O2C3}\mathrm{O2}-\mathrm{C3C2}\mathrm{C3}+\mathrm{C3O1}\mathrm{C3}+\mathrm{C3O2}\mathrm{C3}+\mathrm{C3O3}\mathrm{C3}$
$\frac{d \mathrm{C4}}{d \mathrm{time}}=\mathrm{O2C4}\mathrm{O2}+\mathrm{O3C4}\mathrm{O3}-\mathrm{C4O2}\mathrm{C4}+\mathrm{C4O3}\mathrm{C4}$
$\frac{d \mathrm{C5}}{d \mathrm{time}}=\mathrm{C2C5}\mathrm{C2}-\mathrm{C5C2}\mathrm{C5}$
$\frac{d \mathrm{O1}}{d \mathrm{time}}=\mathrm{C3O1}\mathrm{C3}-\mathrm{O1C3}\mathrm{O1}$
$\frac{d \mathrm{O2}}{d \mathrm{time}}=\mathrm{C3O2}\mathrm{C3}+\mathrm{C4O2}\mathrm{C4}-\mathrm{O2C3}\mathrm{O2}+\mathrm{O2C4}\mathrm{O2}$
$\frac{d \mathrm{O3}}{d \mathrm{time}}=\mathrm{C3O3}\mathrm{C3}+\mathrm{C4O3}\mathrm{C4}-\mathrm{O3C3}\mathrm{O3}+\mathrm{O3C4}\mathrm{O3}$
calcium dynamics
ryanodine receptor
signal transduction
cardiac myocyte
Cardiac Myocyte
cardiac
ryanodine receptors
2007-08-21T10:50:06+12:00
2007-05-25T00:00:00+00:00
James
Lawson
Richard
The new version of this model has been re-coded to remove the reaction element and replace it with a simple MathML description of the model reaction kinetics. This is thought to be truer to the original publication, and information regarding the enzyme kinetics etc will later be added to the metadata through use of an ontology.
The model runs in the PCEnv simulator but gives a flat output.
c.lloyd@auckland.ac.nz
Rebecca
Sitsapesan
The University of Auckland
The Bioengineering Institute
Catherine
Lloyd
May
11371448
Markovian Models of Low and High Activity Levals of Cardiac Ryanodine Receptors
80
2727
2741
keyword
Biophysical Journal
Catherine Lloyd
2007-06-05T10:42:08+12:00
Saftenku et al's 2001 markovian model of low activity levels of cardiac ryanodine receptors.
Cardiac Myocyte
Elena
Saftenku
Gave C1 an initial value of 1.0 - this allows the model to produce a curve, rather than a flat line output. This is still unlikely to be the correct output as the model is supposed to depend on voltage and changing calcium levels.
This is the CellML description of Saftenku et al's 2001 markovian model of low activity levels of cardiac ryanodine receptors.
These models can be run in PCEnv but they give a flat output. I suspect they need to be embedded within a whole cell model in order to give a reasonable output.
closed state 4
C4
closed state 5
C5
closed state 2
C2
closed state 3
C3
Alan
Williams
J
closed state 1
C1
Markovian Models of Low and High Activity Levals of Cardiac Ryanodine Receptors (Low Model)
The University of Auckland, Bioengineering Institute
Catherine
Lloyd
May
2001-06
open state 2
O2
open state 3
O3
open state 1
O1