A model of Na+/H+ exchanger and its central role in regulation of pH and Na+ in cardiac myocytes.

Biophysical Journal
Chae Young ChaAkinori Noma

Abstract

A new kinetic model of the Na(+)/H(+) 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(+)/K(+) pump, background H(+), and Na(+) fluxes. This minimum cell model was validated by reconstructing recovery of pH(i) from acidification, accompanying transient increase in [Na(+)](i) due to NHE activity. Based on this cell model, steady-state relationships among pH(i), [Na(+)](I), and [Ca(2+)](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(+)/K(+) pump was not attributed to a dissipation of the Na(+) gradient across the membrane, but to an increase in indirect H(+) 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.

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Citations

Apr 23, 2013·Journal of Molecular and Cellular Cardiology·Carolina D GarciarenaRichard D Vaughan-Jones
Dec 21, 2016·The Journal of Physiology·Makoto YamaguchiHiroshi Ishiguro
Dec 13, 2017·The Journal of General Physiology·Bradley S LaunikonisD George Stephenson
Sep 12, 2019·Physiological Reviews·S F Pedersen, L Counillon
Sep 4, 2015·Physical Biology·Antônio Márcio RodriguesAntônio-Carlos Guimarães de Almeida
Jul 22, 2021·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Medine Cumhur Cure, Erkan Cure

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