A model of mitochondrial Ca(2+)-induced Ca2+ release simulating the Ca2+ oscillations and spikes generated by mitochondria.
Biophys Chem
; 72(1-2): 111-21, 1998 May 05.
Article
en En
| MEDLINE
| ID: mdl-9652089
Recent evidence underlines a key role of mitochondrial Ca2+ fluxes in cell Ca2+ signalling. We present here a kinetic model simulating the Ca2+ fluxes generated by mitochondria during mitochondrial Ca(2+)-induced Ca2+ release (mCICR) resulting from the operation of the permeability transition pore (PTP). Our model connects the Ca2+ fluxes through the ruthenium redsensitive Ca2+ uniporter, the respiration-dependent and passive H+ fluxes, the rate of oxygen consumption, the movements of weak acids across the mitochondrial membrane, the electrical transmembrane potential (delta psi), and operation of the PTP. We find that two factors are crucial to account for the various mCICR profiles that can be observed experimentally: (i) the dependence of PTP opening and closure on matrix pH (pHi), and (ii) the relative inhibition of the respiratory rate consecutive to PTP opening. The resulting model can simulate irreversible Ca2+ efflux from mitochondria, as well as the genesis of damped or sustained Ca2+ oscillations, and of single Ca2+ spikes. The model also simulates the main features of mCICR, i.e. the threshold-dependence of mCICR triggering, and the all-or-nothing nature of mCICR operation. Our model should appear useful to further mathematically address the consequences of mCICR on the spatiotemporal organisation of Ca2+ signals, as a 'plug-in' module for the existing models of cell Ca2+ signalling.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Calcio
/
Membranas Intracelulares
/
Mitocondrias
/
Modelos Biológicos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Biophys Chem
Año:
1998
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Países Bajos