Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Feb;87(1):397-419.
doi: 10.1146/annurev-physiol-022624-020130.

Chloride-Dependent Cation Transport via SLC12 Carriers at Atomic Resolution

Affiliations
Free article
Review

Chloride-Dependent Cation Transport via SLC12 Carriers at Atomic Resolution

Eric Delpire. Annu Rev Physiol. 2025 Feb.
Free article

Abstract

The SLC12 family of genes encodes electroneutral Cl--dependent cation transporters (i.e., Na-Cl, K-Cl, Na-K-2Cl cotransporters), which play significant roles in maintaining cell and body homeostasis. Recent resolution of their structures at the atomic level provides a new understanding how these transporters operate in health and disease and how they are targeted for therapeutic intervention. Overall, the SLC12 transporter cryo-EM structures confirm some key features established by traditional biochemical and molecular methods, such as the presence of 12 transmembrane domains and the formation of a functional dimer. Study of these structures also uncovers previously unknown features, such as the presence of strategic salt bridges that explain why transporters are stabilized in specific conformations. The cryo-EM structures show similarities with other transport protein structures, especially regarding the position of the cations. The structures also pose challenging questions regarding the number of ions bound and the strict electroneutrality that is conventional understanding.

Keywords: K-Cl cotransporter; Na-Cl cotransporter; Na-K-2Cl cotransporter; loop diuretics; thiazide diuretics.

PubMed Disclaimer

Similar articles

MeSH terms

LinkOut - more resources