Abstract
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.
Original language | English (US) |
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Pages (from-to) | 2223-2235 |
Number of pages | 13 |
Journal | Biophysical journal |
Volume | 67 |
Issue number | 6 |
DOIs | |
State | Published - 1994 |
Bibliographical note
Funding Information:Kenneth W. Spitzer and Timothy J. Lewis provided us with much infor- mation and fruitful discussions during the development of the model presented here. We thank John Stephenson for his critical suggestions for the revision of this work. This research is supported in part by National Institutes of Health grant GM 29123.