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.
Strupp
M
M
Physiologisches Institut, Universität München, Germany.
Staub
F
F
Grafe
P
P
D000138:Acidosis / Q000150:complications / Q000378:metabolism*; D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism; D002118:Calcium / Q000502:physiology*; D004553:Electric Conductivity; D005910:Glioma / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009457:Neuroglia / Q000502:physiology*; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism*; D011802:Quinidine / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured
D015221:Potassium Channels; D011802:Quinidine; D011188:Potassium; D002118:Calcium