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

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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Cha CY,Oka C,Earm YE,Wakabayashi S,Noma A

doi

10.1016/j.bpj.2009.08.053

subject

Has Abstract

pub_date

2009-11-18 00:00:00

pages

2674-83

issue

10

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(09)01444-1

journal_volume

97

pub_type

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