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Updated: Apr 7, 2026

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting
Published on: December 9, 2022
K-Cl cotransporters, cell volume homeostasis, and neurological disease
Kristopher T Kahle1, Arjun R Khanna2, Seth L Alper3
1Department of Neurosurgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02114, USA; Manton Center for Orphan Disease Research, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02114, USA.
Abstract:
K(+)-Cl(-) cotransporters (KCCs) were originally characterized as regulators of red blood cell (RBC) volume. Since then, four distinct KCCs have been cloned, and their importance for volume regulation has been demonstrated in other cell types. Genetic models of certain KCCs, such as KCC3, and their inhibitory WNK-STE20/SPS1-related proline/alanine-rich kinase (SPAK) serine-threonine kinases, have demonstrated the evolutionary necessity of these molecules for nervous system cell volume regulation, structure, and function, and their involvement in neurological disease. The recent characterization of a swelling-activated dephosphorylation mechanism that potently stimulates the KCCs has pinpointed a potentially druggable switch of KCC activity. An improved understanding of WNK/SPAK-mediated KCC cell volume regulation in the nervous system might reveal novel avenues for the treatment of multiple neurological diseases.
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