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• W2107555653 abstract "Our recent study has revealed that 12,14-dichlorodehydroabietic acid (diCl-DHAA), which is synthetically derived from a natural product, abietic acid, is a potent opener of large conductance Ca²⁺-activated K⁺ (BK) channel. Here, we examined, by using a channel expression system in human embryonic kidney 293 cells, the mechanisms underlying the BK channel opening action of diCl-DHAA and which subunit of the BK channel (α or β1) is the site of action for diCl-DHAA. BK channel activity was significantly enhanced by diCl-DHAA at concentrations of 0.1 μM and higher in a concentration-dependent manner. diCl-DHAA enhanced the activity of BKα by increasing sensitivity to both Ca²⁺ and membrane potential without changing the single channel conductance. It is notable that the increase in BK channel open probability by diCl-DHAA showed significant inverse voltage dependence, i.e., larger potentiation at lower potentials. Since coexpression of β1 subunit with BKα did not affect the potency of diCl-DHAA, the site of action for diCl-DHAA is suggested to be BKα subunit. Moreover, kinetic analysis of single channel currents indicates that diCl-DHAA opens BKα mainly by decreasing the time staying in a long closed state. Although reconstituted voltage-dependent Ca²⁺ channel current was significantly reduced by 1 μM diCl-DHAA, BK channels were selectively activated at lower concentrations. These results indicate that diCl-DHAA is one of the most potent BK channel openers acting on BKα and a useful prototype compound to develop a novel BK channel opener." @default.
• W2107555653 created "2016-06-24" @default.
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• W2107555653 date "2005-09-29" @default.
• W2107555653 modified "2023-10-18" @default.
• W2107555653 title "Molecular Mechanisms for Large Conductance Ca²⁺-Activated K⁺ Channel Activation by a Novel Opener, 12,14-Dichlorodehydroabietic Acid" @default.
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• W2107555653 doi "https://doi.org/10.1124/jpet.105.093856" @default.
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