Unconventional chemiosmotic coupling of NHA2, a mammalian Na +/H+ antiporter, to a plasma membrane H+ gradient

Kalyan C. Kondapalli, Laura M. Kallay, Melanie Muszelik, Rajini Rao

Research output: Contribution to journalArticlepeer-review

Abstract

Human NHA2, a newly discovered cation proton antiporter, is implicated in essential hypertension by gene linkage analysis. We show that NHA2 mediates phloretin-sensitive Na+-Li+counter-transport (SLC) activity, an established marker for hypertension. In contrast to bacteria and fungi where H+ gradients drive uptake of metabolites, secondary transport at the plasma membrane of mammalian cells is coupled to the Na +electrochemical gradient. Our findings challenge this paradigm by showing coupling of NHA2 and V-type H+-ATPase at the plasma membrane of kidney-derived MDCK cells, resulting in a virtual Na+ efflux pump. Thus, NHA2 functionally recapitulates an ancient shared evolutionary origin with bacterial NhaA. Although plasma membrane H+ gradients have been observed in some specialized mammalian cells, the ubiquitous tissue distribution of NHA2 suggests that H+-coupled transport is more widespread. The coexistence of Na+ and H+-driven chemiosmotic circuits has implications for salt and pH regulation in the kidney.

Original languageEnglish (US)
Pages (from-to)36239-36250
Number of pages12
JournalJournal of Biological Chemistry
Volume287
Issue number43
DOIs
StatePublished - Oct 19 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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