Mechanism of high K+ and Tl+ uptake in cultured human glioma cells

Summary 1. The aim of this study was to elucidate if the K⁺ uptake was higher in cultured human glioma cells than in cells from other malignant tumors and to analyze the importance of membrane potential and K⁺ channels for the uptake.2. K⁺ transport properties were studied with the isotopes⁴²K and the K-analogue²⁰¹Tl.3. Comparison with cultured cells from other malignant tumors showed that the specific steady-state accumulation of Tl⁺ was significantly higher in glioma cells (U-251MG and Tp-378MG).4. In Ringer's solution at 37°C the rates of K⁺ and Tl⁺ uptake were both inhibited by about 55% in ouabain and 60% in furosemide, bumetanide, or Na⁺-or Cl^–-free medium. This indicated that the routes for K⁺ and Tl⁺ uptake were similar and due to Na,K-ATPase-dependent transport and to Na-K-Cl cotransport.5. About 10% of the uptake was neither ouabain nor bumetanide sensitive. Ba²⁺, which is known to block inward-rectifying K⁺ channels and to depolarize glial cells, and other K⁺ channel blockers (Cs⁺ and bupivacaine), had no effect on Tl⁺ uptake.6. Metabolic inhibition with dinitrophenol reduced the uptake rate to 17%.7. The washout of Tl⁺ was unaffected by bumetanide and K⁺ channel blockers, but dinitrophenol caused a transient increase of 75%, an effect which persisted in the presence of K⁺ channel blockers.8. It was concluded that the high specific K⁺ and Tl⁺ accumulation in cultured human glioma cells was due not to the presence of inwardly rectifying K⁺ channels or other identified K⁺ channels, but to Na,K-ATPase dependent transport and Na-K-Cl cotransport.