Endosomal 2Cl-/H+ exchangers regulate neuronal excitability by tuning Kv7/KCNQ channel density.

ABSTRACT: CLCN3 and CLCN4 encode the endosomal 2Cl-/H+ exchangers ClC-3 and ClC-4, which are highly expressed within the CNS, including the hippocampal formation. Pathogenic variants recently found in these genes have given rise to the rare CLCN3- and CLCN4-related neurodevelopmental conditions, characterized by a range of neurological and neuropsychiatric complications, such as global developmental delay, intellectual disability as a core feature, seizures, behavioural issues and brain abnormalities. The mechanisms by which ClC-3 and ClC-4 regulate neuronal function and viability, in addition to the molecular pathways affected in CLCN3- and CLCN4-related neurodevelopmental conditions, remain unknown. In neurodegenerative diseases, neuronal dendrites undergo pathological changes often associated wit

SUBMITTER: Qi G 

PROVIDER: S-EPMC12677024 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature