dc.contributor.author |
Tran, Kenneth |
en |
dc.contributor.author |
Smith, NP |
en |
dc.contributor.author |
Loiselle, Denis |
en |
dc.contributor.author |
Crampin, Edmund |
en |
dc.date.accessioned |
2011-09-06T03:24:56Z |
en |
dc.date.issued |
2009 |
en |
dc.identifier.citation |
Biophysical Journal 96(5):2029-2042 04 Mar 2009 |
en |
dc.identifier.issn |
0006-3495 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/7785 |
en |
dc.description.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 Ca2+ and pH, and to the metabolites MgATP, MgADP, and Pi. Optimization of model parameters to fit experimental data favors a fully cooperative Ca2+-binding mechanism and predicts a Ca2+/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 Ca2+ dynamics to simulate the effects on the cell of compromised metabolism arising in ischemia and hypoxia. |
en |
dc.language |
EN |
en |
dc.publisher |
Biophysical Society. Elsevier Inc. |
en |
dc.relation.ispartofseries |
Biophysical Journal |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0006-3495/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
RETICULUM CALCIUM-PUMP |
en |
dc.subject |
EXCITATION-CONTRACTION |
en |
dc.subject |
RECONSTITUTED PROTEOLIPOSOMES |
en |
dc.subject |
ADENOSINE-TRIPHOSPHATASE |
en |
dc.subject |
CA2&-DEPENDENT ATPASE |
en |
dc.subject |
VENTRICULAR MYOCYTES |
en |
dc.subject |
STEADY-STATE |
en |
dc.subject |
BINDING |
en |
dc.subject |
TRANSPORT |
en |
dc.subject |
CA-2+ |
en |
dc.title |
A Thermodynamic Model of the Cardiac Sarcoplasmic/Endoplasmic Ca2+ (SERCA) Pump |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.bpj.2008.11.045 |
en |
pubs.issue |
5 |
en |
pubs.begin-page |
2029 |
en |
pubs.volume |
96 |
en |
dc.rights.holder |
Copyright: 2009 the Biophysical Society. |
en |
dc.identifier.pmid |
19254563 |
en |
pubs.end-page |
2042 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
91316 |
en |
pubs.org-id |
Bioengineering Institute |
en |
pubs.org-id |
ABI Associates |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
pubs.record-created-at-source-date |
2010-09-01 |
en |
pubs.dimensions-id |
19254563 |
en |