Components of neuronal chloride transport in rat and human neocortex

Non-technical summary The inhibitory neurotransmitter GABA activates two distinct receptors of which the GABAA receptor is mainly a Cl− conducting ion channel. The proper functioning of inhibition at the GABAA receptor depends on the ionic gradient prevailing during receptor activation, and in epilepsy there is an aberrant Cl− gradient. Using rat and human cortical neurones and pharmacological inhibitors, we calculated the contributions of neuronal Cl− extrusion by the Na+–K+–2Cl− transporter NKCC1, the K+-coupled Cl− transporter KCC2 and the voltage-gated Cl− channel ClC2. We found that KCC2 is the major route of Cl− extrusion and that reduced KCC2 Cl− extrusion is likely to be the initial step of disturbed Cl− regulation. The results contribute to our understanding of epilepsy.