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We studied Cl<jats:sup>\u2212<\/jats:sup> channels in a morphologically distinct subpopulation (\u223c 5% of cells) of small (10\u201312 \u03bcm, 11.8 \u00b1 0.6 pF), phase\u2010dark, GFAP\u2010positive native reactive astrocytes (NRAs) freshly isolated from injured adult rat brains. Their resting potential, \u221257.1 \u00b1 4.0 mV, polarized to \u221272.7 \u00b1 4.5 mV with BAPTA\u2010AM, an intracellular Ca<jats:sup>2+<\/jats:sup> chelator, and depolarized to \u221230.7 \u00b1 6.1 mV with thapsigargin, which mobilizes Ca<jats:sup>2+<\/jats:sup> from intracellular stores. With nystatin\u2010perforated patch clamp, thapsigargin activated a current that reversed near the Cl<jats:sup>\u2212<\/jats:sup> reversal potential, which was blocked by Cl<jats:sup>\u2212<\/jats:sup> channel blockers, 5\u2010nitro\u20102\u2010(3\u2010phenylpropylamino)\u2010benzoate (NPPB) and Zn<jats:sup>2+<\/jats:sup>, by I<jats:sup>\u2212<\/jats:sup> (10 mM), and by chlorotoxin (EC<jats:sub>50<\/jats:sub> = 47 nM). With conventional whole\u2010cell clamp, NPPB\u2010 and Zn<jats:sup>2+<\/jats:sup>\u2010sensitive currents became larger with increasing [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> (10, 150, 300 nM). Single\u2010channel recordings of inside\u2010out patches confirmed Ca<jats:sup>2+<\/jats:sup> sensitivity of the channel and showed open\u2010state conductances of 40, 80, 130, and 180 pS, and outside\u2010out patches confirmed sensitivity to chlorotoxin. In primary culture, small phase\u2010dark NRAs developed into small GFAP\u2010positive bipolar cells with chlorotoxin\u2010sensitive Cl<jats:sub>Ca<\/jats:sub> channels. Imaging with biotinylated chlorotoxin confirmed the presence of label in GFAP\u2010positive cells from regions of brain injury, but not from uninjured brain. Chlorotoxin\u2010tagged cells isolated by flow cytometry and cultured up to two passages exhibit positive labeling for GFAP and vimentin, but not for prolyl 4\u2010hydroxylase (fibroblast), A2B5 (O2A progenitor), or OX\u201042 (microglia). Expression of a novel chlorotoxin\u2010sensitive Cl<jats:sub>Ca<\/jats:sub> channel in a morphologically distinct subpopulation of NRAs distinguishes these cells as a new subtype of reactive astrocyte. GLIA 42:325\u2013339, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.10212","type":"journal-article","created":{"date-parts":[[2003,4,30]],"date-time":"2003-04-30T10:01:40Z","timestamp":1051696900000},"page":"325-339","source":"Crossref","is-referenced-by-count":17,"title":["Chlorotoxin\u2010sensitive Ca<sup>2+<\/sup>\u2010activated Cl<sup>\u2212<\/sup> channel in type R2 reactive astrocytes from adult rat brain"],"prefix":"10.1002","volume":"42","author":[{"given":"Stanislava","family":"Dalton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volodymyr","family":"Gerzanich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingkui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yafeng","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaroslav","family":"Shuba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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