Diosgenin, a plant-derived sapogenin, stimulates Ca2+-activated K+ current in human cortical HCN-1A neuronal cells

The effects of diosgenin (3 beta-hydroxy-5-spirostene), a plant-derived sapogenin, on ion currents in human cortical neurons (HCN-1A) were investigated. In the whole-cell configuration, diosgenin (0.3-30 mu M) increased the amplitude of K+ outward current (I-k). Diosgenin-stimulated I-k was sensitive to inhibition by paxilline (1 mu M), but not by aparnin (200 nM) or glibenclamide (10 mu M). In the cell-attached configuration, diosgenin applied to the bath increased the activity of large-conductance Ca2+-activated K+ (BKCa) channels without altering single-channel conductance. Diosgenin enhanced BKCa-channel activity with an EC50 value of 25 mu M. However, in inside-out patches, diosgenin applied to the intracellular surface had no effect on BKCa-channel activity, while cilostazol or caffeic acid phenethyl ester increased it. As shown with the aid of intracellular Ca2+ measurements, diosgenin elevated intracellular Ca2+ in HCN-1A cells. Western blotting also revealed the presence of the alpha-subunit of Bk-Ca channels in these cells. The sustained stimulation of I-K arises primarily from the diosgenin-induced Ca2+ influx across the cell membrane. The effect of diosgenin on these channels may affect the functional activity of cortical neurons.