{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:31:39Z","timestamp":1791207099815,"version":"4.1.0"},"reference-count":40,"publisher":"Society for Neuroscience","issue":"21","license":[{"start":{"date-parts":[[2001,5,1]],"date-time":"2001-05-01T00:00:00Z","timestamp":988675200000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2000,11,1]]},"abstract":"<jats:p>Chloride (Cl<jats:sup>\u2212<\/jats:sup>) homeostasis is critical for many cell functions including cell signaling and volume regulation. The action of GABA at GABA<jats:sub>A<\/jats:sub>receptors is primarily determined by the concentration of intracellular Cl<jats:sup>\u2212<\/jats:sup>. Developmental regulation of intracellular Cl<jats:sup>\u2212<\/jats:sup>results in a depolarizing response to GABA in immature neocortical neurons and a hyperpolarizing or shunting response in mature neocortical neurons. One protein that participates in Cl<jats:sup>\u2212<\/jats:sup>homeostasis is the neuron-specific K<jats:sup>+<\/jats:sup>\u2013Cl<jats:sup>\u2212<\/jats:sup>cotransporter (KCC2). Thermodynamic considerations predict that in the physiological ranges of intracellular Cl<jats:sup>\u2212<\/jats:sup>and extracellular K<jats:sup>+<\/jats:sup>concentrations, KCC2 can act to either extrude or accumulate Cl<jats:sup>\u2212<\/jats:sup>. To test this hypothesis, we examined KCC2 function in pyramidal cells from rat neocortical slices in mature (18\u201328 d postnatal) and immature (3\u20136 d postnatal) rats. Intracellular Cl<jats:sup>\u2212<\/jats:sup>concentration was estimated from the reversal potential of whole-cell currents evoked by local application of exogenous GABA. Both increasing and decreasing the extracellular K<jats:sup>+<\/jats:sup>concentration resulted in a concomitant change in intracellular Cl<jats:sup>\u2212<\/jats:sup>concentration in neurons from mature rats. KCC2 inhibition by furosemide caused a change in the intracellular Cl<jats:sup>\u2212<\/jats:sup>concentration that depended on the concentration of pipette Cl<jats:sup>\u2212<\/jats:sup>; in recordings with low pipette Cl<jats:sup>\u2212<\/jats:sup>, furosemide lowered intracellular Cl<jats:sup>\u2212<\/jats:sup>, whereas in recordings with elevated pipette Cl<jats:sup>\u2212<\/jats:sup>, furosemide raised intracellular Cl<jats:sup>\u2212<\/jats:sup>. In neurons from neonatal rats, manipulation of extracellular K<jats:sup>+<\/jats:sup>had no effect on intracellular Cl<jats:sup>\u2212<\/jats:sup>concentration, consistent with the minimal KCC2 mRNA levels observed in neocortical neurons from immature animals. These data demonstrate a physiologically relevant and developmentally regulated role for KCC2 in Cl<jats:sup>\u2212<\/jats:sup>homeostasis via both Cl<jats:sup>\u2212<\/jats:sup>extrusion and accumulation.<\/jats:p>","DOI":"10.1523\/jneurosci.20-21-08069.2000","type":"journal-article","created":{"date-parts":[[2018,4,5]],"date-time":"2018-04-05T15:10:31Z","timestamp":1522941031000},"page":"8069-8076","source":"Crossref","is-referenced-by-count":191,"title":["Potassium-Coupled Chloride Cotransport Controls Intracellular Chloride in Rat Neocortical Pyramidal Neurons"],"prefix":"10.1523","volume":"20","author":[{"given":"R. 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