A Model of Na super(+)/H super(+) Exchanger and Its Central Role in Regulation of pH and Na super(+) in Cardiac Myocytes

A new kinetic model of the Na super(+)/H super(+) exchanger (NHE) was developed by fitting a variety of major experimental findings, such as ion-dependencies, forward/reverse mode, and the turnover rate. The role of NHE in ion homeostasis was examined by implementing the NHE model in a minimum cell...

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Bibliographic Details
Published in:Biophysical journal 2009-11, Vol.97 (10), p.2674-2683
Main Authors: Cha, Chae Young, Oka, Chiaki, Earm, Yung E, Wakabayashi, Shigeo, Noma, Akinori
Format: Article
Language:English
Subjects:
Acidification
Dissipation
Exchange
Fittings
Homeostasis
Ion exchangers
Mathematical models
Pumps
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Summary:A new kinetic model of the Na super(+)/H super(+) exchanger (NHE) was developed by fitting a variety of major experimental findings, such as ion-dependencies, forward/reverse mode, and the turnover rate. The role of NHE in ion homeostasis was examined by implementing the NHE model in a minimum cell model including intracellular pH buffer, Na super(+)/K super(+) pump, background H super(+), and Na super(+) fluxes. This minimum cell model was validated by reconstructing recovery of pH sub(i) from acidification, accompanying transient increase in [Na super(+)] sub(i) due to NHE activity. Based on this cell model, steady-state relationships among pH sub(i), [Na super(+)] sub(I), and [Ca super(2+)] sub(i) were quantitatively determined, and thereby the critical level of acidosis for cell survival was predicted. The acidification reported during partial blockade of the Na super(+)/K super(+) pump was not attributed to a dissipation of the Na super(+) gradient across the membrane, but to an increase in indirect H super(+) production. This NHE model, though not adapted to the dimeric behavioral aspects of NHE, can provide a strong clue to quantitative prediction of degree of acidification and accompanying disturbance of ion homeostasis under various pathophysiological conditions.
ISSN:0006-3495
DOI:10.1016/j.bpj.2009.08.053