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Contribution of Anion Transporters to the Acidosis‐Induced Swelling and Intracellular Acidification of Glial Cells
Author(s) -
Ringel Florian,
Chang Raymond C. C.,
Staub Frank,
Baethmann Alexander,
Plesnila Nikolaus
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0750125.x
Subject(s) - intracellular ph , dids , extracellular , bumetanide , acidosis , chemistry , intracellular , cotransporter , biochemistry , biophysics , ion transporter , endocrinology , biology , sodium , membrane , organic chemistry
: This study examines the contribution of anion transporters to the swelling and intracellular acidification of glial cells from an extracellular lactacidosis, a condition well‐known to accompany cerebral ischemia and traumatic brain injury. Suspended C6 glioma cells were exposed to lactacidosis in physiological or anion‐depleted media, and different anion transport inhibitors were applied. Changes in cell volume and intracellular pH (pH i ) were simultaneously quantified by flow cytometry. Extracellular lactacidosis (pH 6.2) led to an increase in cell volume to 125.1 ± 2.5% of baseline within 60 min, whereas the pH i dropped from the physiological value of 7.13 ± 0.05 to 6.32 ± 0.03. Suspension in Cl ‐ ‐free or HCO 3 ‐ /CO 2 ‐free media or application of anion transport inhibitors [0.1 m M bumetanide or 0.5 m M 4,4′‐diisothio‐cyanatostilbene‐2,2′‐disulfonic acid (DIDS)] did not affect cell volume during baseline conditions but significantly reduced cell swelling from lactacidosis. In addition, the Cl ‐ ‐free or HCO 3 ‐ /CO 2 ‐free media and DIDS attenuated intracellular acidosis on extracellular acidification. From these findings it is concluded that besides the known activation of the Na + /H + exchanger, activation of the Na + ‐independent Cl ‐ /HCO 3 ‐ exchanger and the Na + ‐K + ‐Cl ‐ cotransporter contributes to acidosis‐induced glial swelling and the intracellular acidification. Inhibition of these processes may be of interest for future strategies in the treatment of cytotoxic brain edema from cerebral ischemia or traumatic brain injury.