A model of mitochondrial Ca2+-induced Ca2+ release simulating the Ca2+ oscillations and spikes generated by mitochondria
Biophysical Chemistry. 1998-05-01; 72(1-2): 111-121
DOI: 10.1016/S0301-4622(98)00127-6
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Selivanov VA(1), Ichas F, Holmuhamedov EL, Jouaville LS, Evtodienko YV, Mazat JP.
Author information:
(1)GESBI, D(BM)2, Université Victor Segalen, Bordeaux, France.
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.
DOI: 10.1016/s0301-4622(98)00127-6
PMID: 9652089 [Indexed for MEDLINE]