Vestibular Hair Bundles Control pH with (Na+, K+)/H+Exchangers NHE6 and NHE9

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

doi:10.1523/jneurosci.2990-06.2006

Cited by 50 publications

(52 citation statements)

References 50 publications

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“…1 The activities of the K + ,Cl -cotransporter (KCC) and of the cation-proton exchangers in the RBC of CHC patients have not been addressed. K + (Na + )/H + exchange (KNHE), probably mediated by one of the 6-9 isoforms of NHE, 13,14 was earlier observed in human erythrocytes. This K + flux component was most pronounced at low ionic strength and was inhibited by the amiloride derivative HOE-642.…”

Section: Resultsmentioning

confidence: 94%

Cryohydrocytosis: increased activity of cation carriers in red cells from a patient with a band 3 mutation

Bogdanova

Goede²,

Weiss³

et al. 2009

Haematologica

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BackgroundCryohydrocytosis is an inherited dominant hemolytic anemia characterized by mutations in a transmembrane segment of the anion exchanger (band 3 protein). Transfection experiments performed in Xenopus oocytes suggested that these mutations may convert the anion exchanger into a non-selective cation channel. The present study was performed to characterize so far unexplored ion transport pathways that may render erythrocytes of a single cryohydrocytosis patient cation-leaky. Design and MethodsCold-induced changes in cell volume were monitored using ektacytometry and density gradient centrifugation. Kinetics, temperature and inhibitor-dependence of the cation and water movements in the cryohydrocytosis patient's erythrocytes were studied using radioactive tracers and flame photometry. Response of the membrane potential of the patient's erythrocyte membrane to the presence of ionophores and blockers of anion and cation channels was assessed. ResultsIn the cold, the cryohydrocytosis patient's erythrocytes swelled in KCl-containing, but not in NaCl-containing or KNO3-containing media indicating that volume changes were mediated by an anion-coupled cation transporter. In NaCl-containing medium the net HOE-642-sensitive Na + /K + exchange prevailed, whereas in KCl-containing medium swelling was mediated by a chloride-dependent K + uptake. Unidirectional K + influx measurements showed that the patient's cells have abnormally high activities of the cation-proton exchanger and the K + ,Cl -co-transporter, which can account for the observed net movements of cations. Finally, neither chloride nor cation conductance in the patient's erythrocytes differed from that of healthy donors. ConclusionsThese results suggest that cross-talk between the mutated band 3 and other transporters might increase the cation permeability in cryohydrocytosis.

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Section: Resultsmentioning

confidence: 94%

Cryohydrocytosis: increased activity of cation carriers in red cells from a patient with a band 3 mutation

Bogdanova

Goede²,

Weiss³

et al. 2009

Haematologica

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“…It has been documented for several "intracellular" NHE that they can also reside and function on the plasma membrane under certain circumstances, [31][32][33] and dual mitochondrial and plasmalemmal localization has also been reported for the voltage-dependent anion channel VDAC. 34 For the intracellular NHE isoform NHE6, the scaffolding protein RACK1 was recently shown to regulate the balance between plasmalemmal and intracellular localization.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Sodium/Hydrogen Exchanger NHA2

Fuster¹,

Zhang²,

Shi³

et al. 2008

Journal of the American Society of Nephrology

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Cation/proton exchange has been recognized for decades in mammalian mitochondria, but the exchanger proteins have eluded identification. In this study, a cDNA from a human brain library, previously designated NHA2 in the genome, was cloned and characterized. The NHA2 transcript bears more similarity to prokaryotic than known eukaryotic sodium/proton exchangers, but it was found to be expressed in multiple mammalian organs and cultured cells. A mAb to NHA2 was generated and found to label an approximately 55-kD native protein in multiple tissues and cell lines. The specificity of this antibody was confirmed by demonstrating the loss of the native NHA2 band on immunoblots when cultured cells were treated with NHA2-specific small interfering RNA. Although NHA2 protein was detected in multiple organs, within each, its expression was restricted to specific cell types. In the kidney, co-localization with calbindin 28k and reverse transcription-PCR of microdissected tubules revealed that NHA2 is limited to the distal convoluted tubule. In cell lines, native NHA2 was localized both to the plasma membrane and to the intracellular compartment; immunogold electron microscopy of rat distal convoluted tubule demonstrated NHA2 predominantly but not exclusively on the inner mitochondrial membrane. Furthermore, co-sedimentation of NHA2 antigen and mitochondrial membranes was observed with differential centrifugation, and two mitochondrial markers co-localized with NHA2 in cultured cells. Regarding function, human NHA2 reversed the sodium/hydrogen exchanger-null phenotype when expressed in sodium/hydrogen exchanger-deficient yeast and restored the ability to defend high salinity in the presence of acidic extracellular pH. In summary, NHA2 is a ubiquitous mammalian sodium proton/exchanger that is restricted to the distal convoluted tubule in the kidney.

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“…In vestibular hair bundles, for example, both NHE6 and NHE9 are enriched in the plasma membrane where they probably exploit high endolymph K + to efflux cytosolic H + . This mechanism allows the hair cell to remove H + generated by Ca 2+ pumping without ATP hydrolysis in the cell [65]. NHE6 is also highly expressed in the basolateral membrane of osteoblasts, especially in areas of high mineralization, where it helps remove excess H + generated by this process [94].…”

Section: Slc9a6 -Nhe6mentioning

confidence: 99%

“…One exeption to the intracellular localization of NHE9 has thus far been reported. In vestibular hair bundles, NHE9 is (together with NHE6) present in the plasma membrane where it serves to remove cytosolic H + in exchange for endolymph K + [65].…”

Section: Slc9a9 -Nhe9mentioning

confidence: 99%

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Fuster

Alexander

2013

Pflugers Arch - Eur J Physiol

143

122

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The SLC9 gene family encodes Na + /H + exchangers (NHEs). These transmembrane proteins transport ions across lipid bilayers in a diverse array of species from prokaryotes to eukaryotes, including plants, fungi and animals. They utilize the electrochemical gradient of one ion to transport another ion against its electrochemical gradient. Currently, 13 evolutionarily conserved NHE isoforms are known in mammals [46,22,128]. The SLC9 gene family (solute carrier classification of transporters:www.bioparadigms.org) is divided into three subgroups [46]. The SLC9A subgroup encompasses plasmalemmal isoforms NHE1-5 (SLC9A1-5) and the predominantly intracellular isoforms NHE6-9 (SLC9A6-9). The SLC9B subgroup consists of two recently cloned isoforms, NHA1 and NHA2 (SLC9B1 and SLC9B2, respectively). The SLC9C subgroup consist of a sperm specific plasmalemmal NHE (SLC9C1) and a putative NHE, SLC9C2, for which there is currently no functional data [46].NHEs participate in the regulation of cytosolic and organellar pH as well as cell volume. In the intestine and kidney, NHEs are critical for transepithelial movement of Na + and HCO 3 -and thus for whole body volume and acid-base homeostasis [46]. Mutations in the NHE6 or NHE9 genes cause neurological disease in humans and are currently the only NHEs directly linked to human disease.However, it is becoming increasingly apparent that members of this gene family contribute to the pathophysiology of multiple human diseases.

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Vestibular Hair Bundles Control pH with (Na⁺, K⁺)/H⁺Exchangers NHE6 and NHE9

Cited by 50 publications

References 50 publications

Cryohydrocytosis: increased activity of cation carriers in red cells from a patient with a band 3 mutation

Cryohydrocytosis: increased activity of cation carriers in red cells from a patient with a band 3 mutation

Characterization of the Sodium/Hydrogen Exchanger NHA2

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

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