Modulation of Na+/H+ exchange activity by Cl-

Citation
O. Aharonovitz et al., Modulation of Na+/H+ exchange activity by Cl-, AM J P-CELL, 281(1), 2001, pp. C133-C141
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
ISSN journal
0363-6143 → ACNP
Volume
281
Issue
1
Year of publication
2001
Pages
C133 - C141
Database
ISI
SICI code
0363-6143(200107)281:1<C133:MONEAB>2.0.ZU;2-2
Abstract
Na+/H+ exchanger (NHE) activity is exquisitely dependent on the intra- and extracellular concentrations of Na+ and H+. In addition, Cl- ions have been suggested to modulate NHE activity, but little is known about the underlyi ng mechanism, and the Cl- sensitivity of the individual isoforms has not be en established. To explore their Cl- sensitivity, types 1, 2, and 3 Na+/Hexchangers (NHE1, NHE2, and NHE3) were heterologously expressed in antiport -deficient cells. Bilateral replacement of Cl- with nitrate or thiocyanate inhibited the activity of all isoforms. Cl- depletion did not affect cell v olume or the cellular ATP content, which could have indirectly altered NHE activity. The number of plasmalemmal exchangers was unaffected by Cl- remov al, implying that inhibition was due to a decrease in the intrinsic activit y of individual exchangers. Analysis of truncated mutants of NHE1 revealed that the anion sensitivity resides, at least in part, in the COOH-terminal domain of the exchanger. Moreover, readdition of Cl- into the extracellular medium failed to restore normal transport, suggesting that intracellular C l- is critical for activity. Thus interaction of intracellular Cl- with the COOH terminus of NHE1 or with an associated protein is essential for optim al activity.