ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Vestibular hair bundles control pH with (Na+, K+)/H+ exchangers NHE6 and NHE9.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Endosomal system genetics and autism spectrum disorders: A literature review.Neuroscience and biobehavioral reviews · 2016Pooled it
- High-resolution structures of human NHE6 and NHE9 elucidate endosomal ion and lipid interactions.Nature communications · 2026Article
- Integrative structural analysis of human endosomal NHE6 reveals a lipid-associated gate and disordered C-terminus.Nature communications · 2026Article
- The Recycling Endosomal (NaActa physiologica (Oxford, England) · 2026Article
- The Christianson syndrome protein, sodium hydrogen exchanger isoform 6, is required for fat accumulation.The Journal of physiology · 2025Article
- Single Administration of AAV-mAtp6v1b2 Gene Therapy Rescues Hearing and Vestibular Disorders Caused by Atp6v1b2-Induced Lysosomal Dysfunction in Hair Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Missense variants in SLC9A6 cause partial epilepsy without neurodevelopmental delay.Orphanet journal of rare diseases · 2025Article
- Linking endo-lysosomal pH, sterol, and trafficking to neurodegenerative disease.FEMS yeast research · 2025Review
- Roles of Endomembrane Alkali Cation/Proton Exchangers in Synaptic Function and Neurodevelopmental Disorders.Frontiers in physiology · 2022Review
- Emerging links between endosomal pH and cancer.Cancer metastasis reviews · 2020Review
- Sodium-hydrogen exchanger 6 (NHE6) deficiency leads to hearing loss, via reduced endosomal signalling through the BDNF/Trk pathway.Scientific reports · 2020Article
- Sodium Transporters in Human Health and Disease.Frontiers in physiology · 2020Review
- Molecular Composition of Vestibular Hair Bundles.Cold Spring Harbor perspectives in medicine · 2019Review
- The NaMolecular biology of the cell · 2018Article
- A mouse model of autism implicates endosome pH in the regulation of presynaptic calcium entry.Nature communications · 2018Article
- NaThe Journal of physiology · 2017Article
- Article
- The gastric H,K-ATPase in stria vascularis contributes to pH regulation of cochlear endolymph but not to K secretion.BMC physiology · 2016Article
- Mice with conditional deletion of Cx26 exhibit no vestibular phenotype despite secondary loss of Cx30 in the vestibular end organs.Hearing research · 2015Article
- The zebrafish merovingian mutant reveals a role for pH regulation in hair cell toxicity and function.Disease models & mechanisms · 2014Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.