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

  • Daniel G. FusterEmail author
  • R. Todd Alexander
Invited Review


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 [22, 46, 128]. The SLC9 gene family (solute carrier classification of transporters: 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 HCO3 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.


Sodium/hydrogen exchanger NHE SLC9 



We apologize to the many investigators whose work we could not reference due to space limitations. D.F. was supported by a Swiss National Science Foundation grant (# 3100A0-117732), the Swiss National Centre of Competence in Research (NCCR TransCure and NCCR, the Novartis Research Foundation, and by a Medical Research Position Award of the Foundation Prof. Dr. Max Cloëtta. R.T.A is supported by operating funds from the Kidney Foundation of Canada and the Canadian Institute for Health Research (CIHR) as well as a Clinician Scientist Award from CIHR and a Clinical Investigator Award from Alberta Innovates Health Solutions.


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© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Division of Nephrology, Hypertension and Clinical Pharmacology and Institute of Biochemistry and Molecular MedicineUniversity of BernBernSwitzerland
  2. 2.Division of Nephrology, Department of Pediatrics, Faculty of Medicine and DentistryUniversity of AlbertaEdmontonCanada

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