The C6 glioma cell line possesses 5-HT2A receptors that have been shown to increase intracellular calcium levels. We have studied the electrophysiological response of these cells to 5-HT using the whole-cell recording method. Under voltage-clamp, 5-hydroxytryptamine (5-HT) produced an outward current in these cells which was inhibited by extracellularly applied ketanserin and spiperone and by EGTA (10 mM) in the recording electrode. The 5-HT induced response could be mimicked by intracellular photolytic release of inositol (1,4,5) trisphosphate (IP3) from caged molecules. The reversal potentials for the IP3- and 5-HT-induced responses were closely matched. The data indicates that the outward current is likely to be mediated by 5-HT2A receptors stimulating IP3 production which increases intracellular calcium leading to the opening of calcium-activated potassium channels.
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