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The depolarization is due to Cl<jats:sup>\u2212<\/jats:sup> efflux through GABA<jats:sub>A<\/jats:sub> channels; the outward Cl<jats:sup>\u2212<\/jats:sup> gradient is generated by a Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>,2Cl<jats:sup>\u2212<\/jats:sup> cotransporter (NKCC) as first established in amphibians. Using fluorescence imaging microscopy we measured [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> and cell water volume (CWV) in dissociated rat DRG cells (P0\u2013P21) loaded with N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide and calcein, respectively. Basal [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> was 44.2 \u00b1 1.2 mM (mean \u00b1 SE), Cl<jats:sup>\u2212<\/jats:sup> equilibrium potential ( E<jats:sub>Cl<\/jats:sub>) was \u221227.0 \u00b1 0.7 mV ( n = 75). This [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> is about four times higher than electrochemical equilibrium. On isosmotic removal of external Cl<jats:sup>\u2212<\/jats:sup>, cells lost Cl<jats:sup>\u2212<\/jats:sup> and shrank. On returning to control solution, cells reaccumulated Cl<jats:sup>\u2212<\/jats:sup> and recovered CWV. Cl<jats:sup>\u2212<\/jats:sup> reaccumulation had Na<jats:sup>+<\/jats:sup>-dependent (SDC) and Na<jats:sup>+<\/jats:sup>-independent (SIC) components. The SIC stabilized at [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> = 13.2 \u00b1 1.2 mM, suggesting that it was passive ( E<jats:sub>Cl<\/jats:sub> = \u221260.5 \u00b1 3 mV). Bumetanide blocked CWV recovery and most (65%) of the SDC (IC<jats:sub>50<\/jats:sub> = 5.7 \u03bcM), indicating that both were mediated by NKCC. Active Cl<jats:sup>\u2212<\/jats:sup> uptake fell with increasing [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> and became negligible when [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> reached basal levels. The kinetics of active Cl<jats:sup>\u2212<\/jats:sup> uptake suggests a negative feedback system in which intracellular Cl<jats:sup>\u2212<\/jats:sup>regulates its own influx thereby keeping [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> constant, above electrochemical equilibrium but below the value that would attain if NKCC reached thermodynamic equilibrium. <\/jats:p>","DOI":"10.1152\/jn.01007.2007","type":"journal-article","created":{"date-parts":[[2008,4,3]],"date-time":"2008-04-03T01:55:45Z","timestamp":1207187745000},"page":"169-184","source":"Crossref","is-referenced-by-count":88,"title":["Na<sup>+<\/sup>,K<sup>+<\/sup>,2Cl<sup>\u2212<\/sup> Cotransport and Intracellular Chloride Regulation in Rat Primary Sensory Neurons: Thermodynamic and Kinetic Aspects"],"prefix":"10.1152","volume":"100","author":[{"given":"H\u00e9ctor I.","family":"Rocha-Gonz\u00e1lez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihong","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Alvarez-Leefmans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","unstructured":"Alvarez-Leefmans FJ. 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