A Ca(2+)- and pH-dependent K+ channel of rat C6 glioma cells and its possible role in acidosis-induced cell swelling.

The aim of the present study was to explore whether a change in membrane K+ conductance contributes to acidosis-induced swelling of cultured rat C6 glioma cells. Electrophysiological studies were performed using whole-cell and single-channel recordings in combination with cell volume measurements in cell suspension by flow cytometry. Whole-cell recordings revealed a voltage-dependent K+ conductance. The predominant K+ channel in single-channel recordings with symmetrical high K+ concentrations was inwardly rectifying and had conductances of 35 and 15 pS, respectively. A raised internal free Ca2+ concentration and membrane depolarization increased the open probability of this channel. Internal acidosis (pH 6.4-5.4), on the other hand, reduced open probability and single-channel conductance. Both whole-cell and single-channel K+ currents were blocked by quinidine (0.1-1 mM), which was therefore used to analyze the functional consequences of an inhibition of this conductance for cell volume. Thereby, quinidine (1 mM) produced a small (5%) and transient cell swelling of C6 glioma cells. In contrast, acidosis (pH 5.6) caused a much larger (about 20%) and maintained swelling. Since quinidine produced only a minor swelling of C6 cells, it is unlikely that inhibition of the K+ conductance caused acidosis-induced cell swelling. Other mechanisms, such as activation of ion transporters, must therefore be responsible.