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- W4382362651 abstract "Acid-sensing ion channels (ASICs) are proton-gated ion channels that contribute to pain perception and neurotransmission. Being involved in sensing inflammation and ischemia, ASIC1a and ASIC3 are promising drug targets. Polyphenol tannic acid (TA) as well as green tea can interact with a variety of ion channels, but their effect on ASICs remains unknown. In addition, it is unknown whether they interact with ion channels via a common mechanism. Here, we show that TA is a potent modulator of ASICs. TA inhibited the transient current of rat ASIC3 expressed in HEK cells with an apparent IC50 of 2.2 ± 0.6 μM; it potentiated the sustained current and induced a slowly declining decay current. In addition, it produced an acidic shift of the pH-dependent activation of ASIC3 and inhibited the window current at pH 7.0. Moreover, TA inhibited the transient current of ASIC1a, ASIC1b, and ASIC2a. Pentagalloylglucose that is chemically identical to the central part of TA and a green tea extract both had effects on ASIC3 comparable to TA. TA and green tea inhibited inward currents generated by gramicidin channels, indicating interaction with the membrane. These results show that TA, pentagalloylglucose, and green tea modulate ASICs and identify alteration of the membrane as the potential common mechanism of this modulation. These properties will limit clinical application of these molecules." @default.
- W4382362651 created "2023-06-29" @default.
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- W4382362651 date "2023-06-28" @default.
- W4382362651 modified "2023-09-25" @default.
- W4382362651 title "Modulation of Acid-Sensing Ion Channels by Tannic Acid and Green Tea via a Membrane-Mediated Mechanism" @default.
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- W4382362651 doi "https://doi.org/10.1021/acschemneuro.3c00032" @default.
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