Vestibular hair bundles control pH with (Na+, K +)/H+ exchangers NHE6 and NHE9

Jennifer K. Hill, Christopher L. Brett, Anthony Chyou, Laura M. Kallay, Masao Sakaguchi, Rajini Rao, Peter G. Gillespie

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


In hair cells of the inner ear, robust Ca2+/H+ exchange mediated by plasma-membrane Ca2+-ATPase would rapidly acidify mechanically sensitive hair bundles without efficient removal of H +. We found that, whereas the basolateral membrane of vestibular hair cells from the frog saccule extrudes H+ via an Na +-dependent mechanism, bundles rapidly remove H+ in the absence of Na+ and HCO3-, even when the soma is acidified. K+ was fully effective and sufficient for H+ removal; in contrast, Rb+ failed to support pH recovery. Na +/H+-exchanger isoform 1 (NHE1) was present on hair-cell soma membranes and was likely responsible for Na+-dependent H + extrusion. NHE6 and NHE9 are organellar isoforms that can appear transiently on plasma membranes and have been proposed to mediate K +/H+ exchange. We identified NHE6 in a subset of hair bundles; NHE9 was present in all bundles. Heterologous expression of these isoforms in yeast strains lacking endogenous exchangers conferred pH-dependent tolerance to high levels of KCl and NaCl. NHE9 preferred cations in the order K+, Na+ ≫ Rb+, consistent with the relative efficacies of these ions in promoting pH recovery in hair bundles. Electroneutral K+/H+ exchange, which we propose is performed by NHE9 in hair bundles, exploits the high-K+ endolymph, responds only to pH imbalance across the bundle membrane, is unaffected by the +80 mV endocochlear potential, and uses mechanisms already present in the ear for K+ recycling. This mechanism allows the hair cell to remove H+ generated by Ca2+ pumping without ATP hydrolysis in the cell.

Original languageEnglish (US)
Pages (from-to)9944-9955
Number of pages12
JournalJournal of Neuroscience
Issue number39
StatePublished - Sep 27 2006


  • H
  • Hair cells
  • Ion transport
  • Mechanotransduction
  • NHE
  • pH

ASJC Scopus subject areas

  • Neuroscience(all)


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