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

The effects of diosgenin (3β-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 μM) increased the amplitude of K⁺ outward current (I_K). Diosgenin-stimulated I_K was sensitive to inhibition by paxilline (1 μM), but not by apamin (200 nM) or glibenclamide (10 μM). In the cell-attached configuration, diosgenin applied to the bath increased the activity of large-conductance Ca²⁺-activated K⁺ (BK_Ca) channels without altering single-channel conductance. Diosgenin enhanced BK_Ca-channel activity with an EC₅₀ value of 25 μM. However, in inside-out patches, diosgenin applied to the intracellular surface had no effect on BK _Ca-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 α-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.