Diosgenin, a plant-derived sapogenin, stimulates Ca2+-activated K+ current in human cortical HCN-1A neuronal cells.
The effects of diosgenin (3beta-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. -30 microM) increased the amplitude of K+ outward current (I(K)). Diosgenin-stimulated I(K) was sensitive to inhibition by paxilline (1 microM), but not by apamin (200 nM) or glibenclamide (10 muM). 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 microM. 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 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. Abbreviations. I(K):K+ outward current I(K(Ca)):Ca2+-activated K+ current BK(Ca) channel:Large-conductance Ca2+-activated K+ channel CAPE:caffeic acid phenethyl ester [Ca2+] (i):intracellular Ca2+ concentration I/V relationship:current/voltage relationship K (ATP) channel:ATP-sensitive K+ channel K(Ca) channel:Ca2+-activated K+ channel.
Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan, Republic of China.
Ya-Jean
YJ
Wang
Yen-Chin
YC
Liu
Han-Dong
HD
Chang
Sheng-Nan
SN
Wu
D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects; D027742:Dioscorea; D004144:Diosgenin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D008517:Phytotherapy; D012502:Sapogenins / Q000008:administration & dosage / Q000494:pharmacology
D002121:Calcium Channel Blockers; D051036:Large-Conductance Calcium-Activated Potassium Channels; D012502:Sapogenins; D004144:Diosgenin