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

Author:
Jiang, B  Cao, K  Wang, R  


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 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 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 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. (C) 2004 Elsevier B.V All rights reserved.


Page:
93---100


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