title: A thermodynamic model of the cardiac sarcoplasmic/endoplasmic Ca(2+) (SERCA) pump.
abstract: We present a biophysically based kinetic model of the cardiac SERCA pump that consolidates a range of experimental data into a consistent and thermodynamically constrained framework. The SERCA model consists of a number of sub-states with partial reactions that are sensitive to Ca(2+) and pH, and to the metabolites MgATP, MgADP, and Pi. Optimization of model parameters to fit experimental data favors a fully cooperative Ca(2+)-binding mechanism and predicts a Ca(2+)/H(+) counter-transport stoichiometry of 2. Moreover, the order of binding of the partial reactions, particularly the binding of MgATP, proves to be a strong determinant of the ability of the model to fit the data. A thermodynamic investigation of the model indicates that the binding of MgATP has a large inhibitory effect on the maximal reverse rate of the pump. The model is suitable for integrating into whole-cell models of cardiac electrophysiology and Ca(2+) dynamics to simulate the effects on the cell of compromised metabolism arising in ischemia and hypoxia.
authors.affiliation: Auckland Bioengineering Institute, University of Auckland, New Zealand. k.tran@auckland.ac.nz
authors.forename: Kenneth
authors.initials: K
authors.lastname: Tran
authors.forename: Nicolas P
authors.initials: NP
authors.lastname: Smith
authors.forename: Denis S
authors.initials: DS
authors.lastname: Loiselle
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Crampin
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry; D000465:Algorithms; D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D006859:Hydrogen / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051379:Mice; D008956:Models, Chemical; D011485:Protein Binding; D011817:Rabbits; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D000244:Adenosine Diphosphate; D006859:Hydrogen; D000255:Adenosine Triphosphate; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium