In mammalian neurons, cation–chloride cotransporters (CCCs) have vital roles in regulating the intracellular chloride concentration—which in turn determines the strength and polarity of γ-aminobutyric-acid-mediated neurotransmission—and in cell volume homeostasis. In this Review, Kahle et al. consider how breakdowns of chloride homeostasis resulting from alterations in CCC activity might contribute to various neurological disorders, including seizures and neuropathic pain, and they discuss the potential of CCCs as targets for novel therapeutic strategies.
- Kristopher T Kahle
- Kevin J Staley
- David B Mount