Comparison of simulated and measured calcium sparks in intact skeletal muscle fibers of the frog
Catherine
Lloyd
Auckland Bioengineering Institute, The University of Auckland
Model Status
This CellML model runs in OpenCell and COR and the units are consistent. There are no simple figures of concentration against time in the publication to compare the CellML model simulation output against.
Model Structure
ABSTRACT: Calcium sparks in frog intact skeletal muscle fibers were modeled as stereotypical events that arise from a constant efflux of Ca(2+) from a point source for a fixed period of time (e.g., 2.5 pA of Ca(2+) current for 4.6 ms; 18 degrees C). The model calculates the local changes in the concentrations of free Ca(2+) and of Ca(2+) bound to the major intrinsic myoplasmic Ca(2+) buffers (troponin, ATP, parvalbumin, and the SR Ca(2+) pump) and to the Ca(2+) indicator (fluo-3). A distinctive feature of the model is the inclusion of a binding reaction between fluo-3 and myoplasmic proteins, a process that strongly affects fluo-3's Ca(2+)-reaction kinetics, its apparent diffusion constant, and hence the morphology of sparks. DeltaF/F (the change in fluo-3's fluorescence divided by its resting fluorescence) was estimated from the calculated changes in fluo-3 convolved with the microscope point-spread function. To facilitate comparisons with measured sparks, noise and other sources of variability were included in a random repetitive fashion to generate a large number of simulated sparks that could be analyzed in the same way as the measured sparks. In the initial simulations, the binding of Ca(2+) to the two regulatory sites on troponin was assumed to follow identical and independent binding reactions. These simulations failed to accurately predict the falling phase of the measured sparks. A second set of simulations, which incorporated the idea of positive cooperativity in the binding of Ca(2+) to troponin, produced reasonable agreement with the measurements. Under the assumption that the single channel Ca(2+) current of a ryanodine receptor (RYR) is 0.5-2 pA, the results suggest that 1-5 active RYRs generate an average Ca(2+) spark in a frog intact muscle fiber.
The original paper reference is cited below:
Comparison of simulated and measured calcium sparks in intact skeletal muscle fibers of the frog, S.M. Baylor, S. Hollingworth and W.K. Chandler, 2002, Journal of General Physiology, 120, 349-368. PubMed ID: 12198091
Schematic diagrams of the Ca2+ binding reactions for various buffers and indicators: A The reaction of Ca2+ with ATP in the presence of free Mg2+, B Reaction of Ca2+ with protein (Pr) and fluo-3 (Fluo), C Competitive reaction of Ca2+ and Mg2+ with parvalbumin (Parv), D Binding reaction of Ca2+ binding and transport by the sarcoplasmic reticulum Ca2+ pump (E), E One-step reaction of Ca2+ with Troponin (Trop), and F Two-step reaction of Ca2+ with Troponin (Trop).
skeletal muscle
calcium dynamics
keyword
2009-05-05T12:09:12+12:00
Comparison of Simulated and Measured Calcium Sparks in Intact Skeletal Muscle Fibers of the Frog (Reaction B)
The University of Auckland, Auckland Bioengineering Institute
James
Lawson
Richard
updated curation status
Journal of General Physiology
2007-06-05T09:15:26+12:00
Catherine
Lloyd
May
This is the CellML description of Baylor, Hollingworth and Chandler's
2002 model of the Ca2+-ATP binding reaction in skeletal myocytes.
Catherine Lloyd
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/almost flat output.
2007-05-23T00:00:00+00:00
Comparison of Simulated and Measured Calcium Sparks in Intact Skeletal Muscle Fibers of the Frog
120
349
368
12198091
W
Chandler
K
c.lloyd@auckland.ac.nz
The University of Auckland
Auckland Bioengineering Institute
Catherine
Lloyd
May
S
Hollingworth
2002-09-01
Baylor, Hollingworth and Chandler's 2002 model of the Ca2+-ATP binding
reaction in skeletal myocytes.
Skeletal Myocyte
Frog
S
Baylor
M