K+/Cl- Cotransporter 2
K+/Cl- cotransporter 2 (KCC2, SLC12A5) is a neuron specific membrane protein that is responsible for the maintenance of the low intracellular Cl- concentration in adult neurons. It is one of four members of the solute carrier 12 (SLC12) family of electroneutral cation-chloride cotransporters and is expressed in most mature mammalian central neurons. KCC2 maintains the intracellular Cl- concentration by using energy from the electrochemical K+ gradient across the plasma membrane to drive Cl- efflux from the cell.
KCC2 has a key role in GABAA and glycine signaling, since low intracellular Cl- concentrations are necessary for the generation of inhibitory post-synaptic potentials (IPSPs) by GABAA and glycine receptors. Modulation of KCC2 function may therefore impact the effectiveness of GABA signaling. Indeed, prolonged intense neuronal firing, as seen in pathological conditions such as epilepsy, spinal cord injury or neuropathic pain, results in down-regulation of KCC2 and affects GABA signaling. Activation of KCC2 has been shown to alleviate pain in a rat model.
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Literature for K+/Cl- Cotransporter 2
Written by Ian Martin, Norman Bowery and Susan Dunn, this review provides a history of the GABA receptor, as well as discussing the structure and function of the various subtypes and the clinical potential of receptor modulators; compounds available from Tocris are listed.Request copy | Download PDF | View all reviews
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