The European and Japanese eel NaCl cotransporter β exhibit chloride currents and are resistant to thiazide type diuretics.

The thiazide-sensitive Na+-Cl- cotransporter (NCC) is the major pathway for salt reabsorption in the mammalian distal convoluted tubule, and the inhibition of its function with thiazides is widely used for the treatment of arterial hypertension. In mammals and teleosts, NCC is present as one ortholog that is mainly expressed in the kidney. One exception, however, is the eel, which has two genes encoding NCC. The eNCCa is located in the kidney and eNCCb, which is present in the apical membrane of the rectum. Interestingly, the European eNCCb functions as a NaCl cotransporter that is nevertheless resistant to thiazides and is not activated by low-chloride hypotonic stress. However, in the Japanese eel rectal sac, a thiazide-sensitive NaCl transport mechanism has been described. The protein sequences between eNCCβ and jNCCβ are 98% identical. Here, by site-directed mutagenesis, we transformed eNCCβ into jNCCβ. Our data showed that jNCCβ, similar to eNCCβ, is resistant to thiazides. In addition, both NCCβ proteins have high transport capacity with respect to their renal NCC orthologs, and in contrast to known NCCs, exhibit electrogenic properties that are reduced when residue I172 is substituted by A, G or M. This is considered a key residue for the chloride ion-binding sites of NKCC and KCC. We conclude that NCCb proteins are not sensitive to thiazides and have electrogenic properties dependent on Cl-, and site I172 is important for the function of NCCβ.

• Publication year

  2022

• Venue

  American Journal of Physiology - Cell Physiology

• Publication date

  2022-06-27

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1152/ajpcell.00213.2022PMID 35759442PMCID PMC9359660
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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