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Biophys. J. BioFAST: First Published September 16, 2005. doi:10.1529/biophysj.105.062984
© 2005 by the Biophysical Society.

A more recent version of this article appeared on December 1, 2005.
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BIOPHYSICAL THEORY AND MODELING

Stabilizing role of calcium store-dependent plasma membrane calcium channels in action potential firing and intracellular calcium oscillations

Martijn Kusters 1, Marc Dernsion 1, Wilbert van Meerwijk 1, Dirk L Ypey 2, Alexander Theuvenet 1 and Stan Gielen 1*

1 Radboud University Nijmegen
2 LUMC

* To whom correspondence should be addressed. E-mail: s.gielen{at}science.ru.nl.

Submitted on March 15, 2005
Revised on April 28, 2005
Accepted on 19 August 2005


  Abstract
In many biological systems cells display spontaneous Ca-oscillations (CaOs) and repetitive action potential (AP) firing. These phenomena have been described separately by models for intracellular IP3-receptor mediated CaOs and for plasma membrane excitability. In this study we describe a model that combines an excitable membrane with an IP3-mediated intracellular calcium oscillator. The IP3-receptor is described as a Ca-channel with open and close probabilities that depend on the cytoplasmic concentration of IP3 and Ca2+. We show that simply combining this model for intracellular CaOs with a recently published model for membrane excitability of normal rat kidney (NRK) fibroblast leads to instability of intracellular Ca-dynamics. In order to guarantee stable long-term periodic firing of APs and CaOs, it is essential to incorporate store-operated-calcium (SOC) channels in addition to the L-type calcium channels. For low IP3-concentrations the cell is at rest at -70 mV. For higher IP3-concentrations the CaOs become activated and trigger repetitive firing of action potentials. At high IP3-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 SOC channels is essential for any cell in which calcium signaling by intracellular CaOs involves both ER and plasma membrane calcium fluxes.

Key Words: Action potential, Calcium oscillation, NRK fibroblast, inositol 1,4,5-trisphosphate receptor




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Copyright © 2005 by the Biophysical Society.