A Biophysically Based Mathematical Model for the Kinetics of Mitochondrial Na+-Ca2+ Antiporter

作者：Pradhan Ranjan K; Beard Daniel A; Dash Ranjan K^*

来源：Biophysical Journal, 2010, 98(2): 218-230.

DOI：10.1016/j.bpj.2009.10.005

Sodium-calcium antiporter is the primary efflux pathway for Ca2+ in respiring mitochondria, and hence plays an important role in mitochondrial Ca2+ homeostasis. Although experimental data on the kinetics of Na+-Ca2+ antiporter are available, the structure and composition of its functional unit and kinetic mechanisms associated with the Na+-Ca2+ exchange (including the stoichiometry) remains unclear. To gain a quantitative understanding of mitochondrial Ca2+ homeostasis, a biophysical model of Na+-Ca2+ 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 Ca2+ handling and bioenergetics; to understand the mechanisms by which Ca2+ plays a role in mitochondrial signaling pathways and energy metabolism.

• 出版日期2010-1-20