Contribution of anion transporters to the acidosis-induced swelling and intracellular acidification of glial cells

This study examines the contribution of anion transporters to the swelling and intracellular acidification of glial cells from an extracellular lactac idosis, a condition well-known to accompany cerebral ischemia and traumatic brain injury. Suspended C6 glioma cells were exposed to lactacidosis in ph ysiological or anion-depleted media, and different anion transport inhibito rs were applied, Changes in cell volume and intracellular pH (pH(i)) were s imultaneously 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, dropped from the physiological value of 7.13 +/- 0 .05 to 6.32 +/- 0.03, Suspension in Cl--free or HCO3-/CO2-free media or app lication of anion transport inhibitors 0.1 mM bumetanide or 0.5 mM 4,4'-dii sothiocyanatostilbene-2,2'-disulfonic acid (DIDS)I did not affect cell volu me during baseline conditions but significantly reduced cell swelling from lactacidosis. In addition, the Cl--free or HCO3-/CO2-free media and DIDS at tenuated intracellutar acidosis on extracellular acidification. From these findings it is concluded that besides the known activation of the Na+/H+ ex changer, activation of the Na+-independent Cl-/HCO3- exchanger and the Na+- K+-Cl- cotransporter contributes to acidosis-induced glial swelling and the intracellular acidification. Inhibition of these processes may be of inter est for future strategies in the treatment of cytotoxic brain edema from ce rebral ischemia or traumatic brain injury.