Model Status
This model is known to run in OpenCell and COR to reproduce the output shown in the publication. The units have been checked and they are consistent.
Model Structure
Abstract: The determinants of relaxation in cardiac muscle are poorly understood, yet compromised relaxation accompanies various pathologies and impaired pump function. In this study, we develop a model of active contraction to elucidate the relative importance of the [Ca2+]i transient magnitude, the unbinding of Ca2+ from troponin C (TnC), and the length-dependence of tension and Ca2+ sensitivity on relaxation. Using the framework proposed by one of our researchers, we extensively reviewed experimental literature, to quantitatively characterize the binding of Ca2+ to TnC, the kinetics of tropomyosin, the availability of binding sites, and the kinetics of crossbridge binding after perturbations in sarcomere length. Model parameters were determined from multiple experimental results and modalities (skinned and intact preparations) and model results were validated against data from length step, caged Ca2+, isometric twitches, and the half-time to relaxation with increasing sarcomere length experiments. A factorial analysis found that the [Ca2+]i transient and the unbinding of Ca2+ from TnC were the primary determinants of relaxation, with a fivefold greater effect than that of length-dependent maximum tension and twice the effect of tension-dependent binding of Ca2+ to TnC and length-dependent Ca2+ sensitivity. The affects of the [Ca2+]i transient and the unbinding rate of Ca2+ from TnC were tightly coupled with the effect of increasing either factor, depending on the reference [Ca2+]i transient and unbinding rate.
model diagram
Schematic diagram depicting the relationships of the active contraction framework proposed by Hunter et al. (11). The model is driven by SL and sarcomere velocity, and intracellular [Ca2+]i. Inputs are in bold, algebraic length dependencies are in italics, processes described by differential equations are standard font.
The original publication reference is cited below:
A Quantitative Analysis of Cardiac Myocyte Relaxation: A Simulation Study, Steven Niederer, Peter Hunter, Nicholas Smith, 2006
Biophysical Journal, 90 1697-1722 PubMed ID: 16339881
Auckland Bioengineering Institute
j.terkildsen@auckland.ac.nz
This is a CellML description of Niederer et al.'s computational model of cardiac myocyte relaxation as described in the 2006 paper "A quantitative analysis of cardiac myocyte relaxation: a simulation study"
N
Smith
P
P
Hunter
J
added cmeta id to T_0 variable
James Lawson
James Lawson
A quantitative analysis of cardiac myocyte relaxation: a simulation study
90(5)
1697
1722
1000
10000
0.1
The University of Auckland
Auckland Bioengineering Institute
Jonna
Terkildsen
16339881
S
Niederer
A
James
Lawson
Richard
Biophysical Journal
2008-08-05T10:32:30+12:00
keyword
cardiac myocyte
endocrine
electrophysiology
relaxation
excitation-contraction coupling
This model can be simulated in COR and PCEnv and is able to reproduce the results published in Niederer et al.'s 2006 paper.
2008-01-07T00:00:00+00:00
2006-03-01 00:00