Abstract

SummaryTwo electron‐neutral, cation‐chloride cotransporters control intraneuronal chloride ion concentration (Cl−). The Na‐K‐2Cl cotransporter‐1 mediates Cl− influx while the K‐Cl cotransporter‐2 (KCC2) extrudes Cl−, assuring that γ‐aminobutyric acid (GABA)ergic signals hyperpolarize neurons. KCC2 is downregulated in pyramidal cells from human temporal lobe epilepsy and experimental focal epilepsy, inducing a depolarizing shift in response to GABA. For an expanded treatment of this topic see Jasper’s Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado‐Escueta AV, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at http://www.ncbi.nlm.nih.gov/books).

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