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Stabilizing Role of Calcium Store-Dependent Plasma Membrane Calcium Channels in Action-Potential Firing and Intracellular Calcium Oscillations
In many biological systems, cells display spontaneous calcium oscillations (CaOs) and repetitive action-potential firing. These phenomena have been described separately by models for intracellular inositol trisphosphate (IP 3)-mediated CaOs and for plasma membrane excitability. In this study, we pre...
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Published in: | Biophysical journal 2005-12, Vol.89 (6), p.3741-3756 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | In many biological systems, cells display spontaneous calcium oscillations (CaOs) and repetitive action-potential firing. These phenomena have been described separately by models for intracellular inositol trisphosphate (IP
3)-mediated CaOs and for plasma membrane excitability. In this study, we present an integrated model that combines an excitable membrane with an IP
3-mediated intracellular calcium oscillator. The IP
3 receptor is described as an endoplasmic reticulum (ER) calcium channel with open and close probabilities that depend on the cytoplasmic concentration of IP
3 and Ca
2+. We show that simply combining this ER model for intracellular CaOs with a model for membrane excitability of normal rat kidney (NRK) fibroblasts leads to instability of intracellular calcium dynamics. To ensure stable long-term periodic firing of action potentials and CaOs, it is essential to incorporate calcium transporters controlled by feedback of the ER store filling, for example, store-operated calcium channels in the plasma membrane. For low IP
3 concentrations, our integrated NRK cell model is at rest at −70
mV. For higher IP
3 concentrations, the CaOs become activated and trigger repetitive firing of action potentials. At high IP
3 concentrations, the basal intracellular calcium concentration becomes elevated and the cell is depolarized near −20
mV. These predictions are in agreement with the different proliferative states of cultures of NRK fibroblasts. We postulate that the stabilizing role of calcium channels and/or other calcium transporters controlled by feedback from the ER store is essential for any cell in which calcium signaling by intracellular CaOs involves both ER and plasma membrane calcium fluxes. |
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ISSN: | 0006-3495 1542-0086 |
DOI: | 10.1529/biophysj.105.062984 |