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• W4225137046 abstract "Large-conductance calcium-regulated potassium channel (BKCa) is known to play an important role in physiological and pathological processes. Despite the BKCa channel being encoded by one gene, this channel has been found to be located not only in the cell membrane but also in the membranes of intracellular compartments, such as in the inner mitochondrial membrane. With some differences, the mitochondrial BKCa (mitoBKCa) channel has been shown to be activated or inhibited by both synthetic and natural compounds. One of them, paxilline, has been considered to be a canonical blocker of this channel. In the previous study, we showed that the natural origin substance quercetin activates the mitoBKCa channel at ten times lower the concentration compared to channel present in the plasma membrane. Here, using the patch-clamp technique, we report that after inhibition of mitoBKCa channels by paxilline, quercetin activates these channels, indicating a paxilline and quercetin binding competition in the regulation of the mitoBKCa channel. To support our hypothesis, we used an analog of quercetin - isorhamnetin, a substance with one substituent changed. Isorhamnetin has no effect on the mitoBKCa channel activity, and after its application, paxilline fully inhibits the channel. Additionally, the molecular modeling studies were used. The results of docking quercetin and paxilline to the BKCa channel suggest that paxilline cannot bind after activation of the channel with quercetin. It seems that the likely mechanism of this phenomenon is the formation of spatial hindrance by quercetin. The results obtained shed a completely new, groundbreaking in the paxilline context, light on the current knowledge about mitochondrial potassium channel regulation." @default.
• W4225137046 created "2022-05-01" @default.
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• W4225137046 date "2022-07-01" @default.
• W4225137046 modified "2023-10-17" @default.
• W4225137046 title "Flavonoid quercetin abolish paxilline inhibition of the mitochondrial BKCa channel" @default.
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• W4225137046 doi "https://doi.org/10.1016/j.mito.2022.04.005" @default.
• W4225137046 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35504559" @default.
• W4225137046 hasPublicationYear "2022" @default.
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