Components of neuronal chloride transport in rat and human neocortex

Non‐technical summary  The inhibitory neurotransmitter GABA activates two distinct receptors of which the GABA A receptor is mainly a Cl − conducting ion channel. The proper functioning of inhibition at the GABA A 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.