Inhibitory effect of protopine on K(ATP) channel subunits expressed in HEK-293 cells.
Protopine is an isoquinoline alkaloid purified from Corydalis tubers and other families of medicinal plants. The purpose of the present study was to investigate the effects of protopine on K(ATP) channels and big conductance (BKCa) channels. Protopine concentration-dependently inhibited K(ATP) channel currents in human embryonic kidney cells (HEK-293) which were cotransfected with Kir6.1 and sulfonylurea receptor 1 (SUR1) subunits, but not that with Kir6.1 cDNA transfection alone. At 25 muM, protopine reversibly decreased Kir6.1/SUR1 currents densities from -17.4+/-3 to -13.2+/-2.4 pA/pF at -60 mV (n=5, P<0.05). The heterologously expressed mSlo-encoded BK(Ca) channel currents in HEK-293 cells were not affected by protopine (25 muM), although iberiotoxin (100 nM) significantly inhibited the expressed BK(Ca) currents (n=5, P<0.05). In summary, protopine selectively inhibited K(ATP) channels by targeting on SUR1 subunit. This discovery may help design specific agents to selectively modulate the function of Kir6.1/SUR1 channel complex and facilitate the understanding of the structure-function relationship of specific subtype of K(ATP) channels.
Jiang
Bo
B
Department of Physiology, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan, S7N 5E5, Canada.
Cao
Kun
K
Wang
Rui
R
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects* / Q000235:genetics; D053119:Benzophenanthridines; D001600:Berberine Alkaloids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D054086:KATP Channels; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects* / Q000235:genetics
D018528:ATP-Binding Cassette Transporters; D053119:Benzophenanthridines; D001600:Berberine Alkaloids; D054086:KATP Channels; D010975:Platelet Aggregation Inhibitors; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; C009093:protopine