{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:03:55Z","timestamp":1791216235427,"version":"4.1.0"},"reference-count":77,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2010,4,30]],"date-time":"2010-04-30T00:00:00Z","timestamp":1272585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2010,5]]},"abstract":"<jats:p>GABAergic excitatory [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>transients can be readily evoked in the mature rat hippocampus by intense activation of GABA<jats:sub>A<\/jats:sub>receptors (GABA<jats:sub>A<\/jats:sub>Rs). Here we show that these [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>responses induced by high\u2010frequency stimulation or GABA<jats:sub>A<\/jats:sub>agonist application are generated by the neuronal K<jats:sup>+<\/jats:sup>\u2013Cl<jats:sup>\u2212<\/jats:sup>cotransporter KCC2 and that the transporter\u2010mediated KCl extrusion is critically dependent on the bicarbonate\u2010driven accumulation of Cl<jats:sup>\u2212<\/jats:sup>in pyramidal neurons. The mechanism underlying GABAergic [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>transients was studied in CA1 stratum pyramidale using intracellular sharp microelectrodes and extracellular ion\u2010sensitive microelectrodes. The evoked [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>transients, as well as the associated afterdischarges, were strongly suppressed by 0.5\u20131 m<jats:sc>m<\/jats:sc>furosemide, a KCl cotransport inhibitor. Importantly, the GABA<jats:sub>A<\/jats:sub>R\u2010mediated intrapyramidal accumulation of Cl<jats:sup>\u2212<\/jats:sup>, as measured by monitoring the reversal potential of fused IPSPs, was unaffected by the drug. It was further confirmed that the reduction in the [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>transients was not due to effects of furosemide on the Na<jats:sup>+<\/jats:sup>\u2010dependent K<jats:sup>+<\/jats:sup>\u2010Cl<jats:sup>\u2212<\/jats:sup>cotransporter NKCC1 or on intraneuronal carbonic anhydrase activity. Blocking potassium channels by Ba<jats:sup>2+<\/jats:sup>enhanced [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>transients whereas pyramidal cell depolarizations were attenuated in further agreement with a lack of contribution by channel\u2010mediated K<jats:sup>+<\/jats:sup>efflux. The key role of the GABA<jats:sub>A<\/jats:sub>R channel\u2010mediated anion fluxes in the generation of the [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>transients was examined in experiments where bicarbonate was replaced with formate. This anion substitution had no significant effect on the rate of Cl<jats:sup>\u2212<\/jats:sup>accumulation, [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>response or afterdischarges. Our findings reveal a novel excitatory mode of action of KCC2 that can have substantial implications for the role of GABAergic transmission during ictal epileptiform activity.<\/jats:p>","DOI":"10.1113\/jphysiol.2009.181826","type":"journal-article","created":{"date-parts":[[2010,3,9]],"date-time":"2010-03-09T04:44:27Z","timestamp":1268109867000},"page":"1527-1540","source":"Crossref","is-referenced-by-count":197,"title":["The K<sup>+<\/sup>\u2013Cl<sup>\u2212<\/sup>cotransporter KCC2 promotes GABAergic excitation in the mature rat 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