A model of calcium dynamics in cardiac myocytes based on the kinetics of ryanodine-sensitive calcium channels

The ryanodine-sensitive calcium channels are pivotal to signal transduction and cell function in many cell types, including cardiac myocytes. In this paper a kinetic model is proposed for these channels. In the model there are two Ca regulatory sites on the channel protein, one positive and the othe...

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Bibliographic Details
Published in:Biophysical journal 1994-12, Vol.67 (6), p.2223-2235
Main Authors: Tang, Y., Othmer, H.G.
Format: Article
Language:English
Subjects:
Adaptation, Physiological
Animals
Binding Sites
Biophysical Phenomena
Biophysics
Calcium - metabolism
Calcium Channels - metabolism
Inositol 1,4,5-Trisphosphate - metabolism
Ion Transport
Kinetics
Mathematics
Models, Biological
Models, Cardiovascular
Muscle Proteins - metabolism
Myocardium - metabolism
Ryanodine - metabolism
Ryanodine Receptor Calcium Release Channel
Sarcoplasmic Reticulum - metabolism
Space life sciences
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Summary:The ryanodine-sensitive calcium channels are pivotal to signal transduction and cell function in many cell types, including cardiac myocytes. In this paper a kinetic model is proposed for these channels. In the model there are two Ca regulatory sites on the channel protein, one positive and the other negative. Cytoplasmic Ca binds to these regulatory sites independently It is assumed that the binding of Ca to the positive site is a much faster process than binding to the negative site. At steady state, the channel opening as a function of the Ca concentration is a bell-shaped curve. The model predicts the adaptation of channels to constant Ca stimulus. When this model is applied to cardiac myocytes, it predicts excitability with respect to Ca perturbations, smoothly graded responses, and Ca oscillations in certain pathological circumstances. In a spatially distributed system, traveling Ca waves in individual myocytes exist under certain conditions. This model can also be applied to other systems where the ryanodine-sensitive channels have been identified.
ISSN:0006-3495
1542-0086
DOI:10.1016/S0006-3495(94)80707-6