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Inhibitory effect of protopine on KATP channel subunits expressed in HEK-293 cells

Author:
Bo Jiang   Kun Cao   Rui Wang  


Journal:
European Journal of Pharmacology


Issue Date:
2004


Abstract(summary):

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 KATP channels and big conductance (BKCa) channels. Protopine concentration-dependently inhibited KATP 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 BKCa channel currents in HEK-293 cells were not affected by protopine (25 muM), although iberiotoxin (100 nM) significantly inhibited the expressed BKCa currents (n=5, P<0.05). In summary, protopine selectively inhibited KATP 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 KATP channels. Copyright 2004 Elsevier B.V All rights reserved.


Page:
93-100


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