A biophysically based mathematical model for the kinetics of mitochondrial Na+-Ca2+ antiporter. Biophys J 2010 Jan 20;98(2):218-30
Date
03/27/2010Pubmed ID
20338843Pubmed Central ID
PMC2808480DOI
10.1016/j.bpj.2009.10.005Scopus ID
2-s2.0-77049095167 (requires institutional sign-in at Scopus site) 24 CitationsAbstract
Sodium-calcium antiporter is the primary efflux pathway for Ca(2+) in respiring mitochondria, and hence plays an important role in mitochondrial Ca(2+) homeostasis. Although experimental data on the kinetics of Na(+)-Ca(2+) antiporter are available, the structure and composition of its functional unit and kinetic mechanisms associated with the Na(+)-Ca(2+) exchange (including the stoichiometry) remains unclear. To gain a quantitative understanding of mitochondrial Ca(2+) homeostasis, a biophysical model of Na(+)-Ca(2+) antiporter is introduced that is thermodynamically balanced and satisfactorily describes a number of independent data sets under a variety of experimental conditions. The model is based on a multistate catalytic binding mechanism for carrier-mediated facilitated transport and Eyring's free energy barrier theory for interconversion and electrodiffusion. The model predicts the activating effect of membrane potential on the antiporter function for a 3Na(+):1Ca(2+) electrogenic exchange as well as the inhibitory effects of both high and low pH seen experimentally. The model is useful for further development of mechanistic integrated models of mitochondrial Ca(2+) handling and bioenergetics to understand the mechanisms by which Ca(2+) plays a role in mitochondrial signaling pathways and energy metabolism.
Author List
Pradhan RK, Beard DA, Dash RKAuthor
Ranjan K. Dash PhD Professor in the Biomedical Engineering department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AlgorithmsAnimals
Calcium
Cattle
Databases, Factual
Diffusion
Homeostasis
Hydrogen-Ion Concentration
Kinetics
Membrane Potential, Mitochondrial
Mitochondria
Models, Chemical
Protein Binding
Rabbits
Reproducibility of Results
Sodium-Calcium Exchanger
Thermodynamics
