Flavonoids as Modulators of Potassium Channels

Richter, Monika; Trybek, Paulina; Delfino, Domenico Vittorio; Wawrzkiewicz-Jałowiecka, Agata

doi:10.3390/ijms24021311

Cited by 7 publications

(3 citation statements)

References 221 publications

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“… 2021 , 2022 ; Richter-Laskowska et al. 2023 ). Quercetin, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one, is a flavonoid commonly found in various fruits, vegetables, and grains.…”

Section: Introductionmentioning

confidence: 99%

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The cross-correlation-based analysis to digest the conformational dynamics of the mitoBK channels in terms of their modulation by flavonoids

Wawrzkiewicz-Jałowiecka

Trybek

Dworakowska

et al. 2023

Eur Biophys J

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The activity of mitochondrial large-conductance voltage- and $$Ca^{2+}$$ C a 2 + -activated $$K^+$$ K + channels (mitoBK) is regulated by a number of biochemical factors, including flavonoids. In particular, naringenin (Nar) and quercetin (Que) reached reasonable scientific attention due to their well-pronounced channel-activating effects. The open-reinforcing outcomes of Nar and Que on the mitoBK channel gating have been already reported. Nevertheless, the molecular picture of the corresponding channel–ligand interactions remains still to be revealed. In this work, we investigate the effects of the Nar and Que on the conformational dynamics of the mitoBK channel. In this aim, the cross-correlation-based analysis of the single-channel signals recorded by the patch-clamp method is performed. The obtained results in the form of phase space diagrams enable us to visually monitor the effects exerted by the considered flavonoids at the level of temporal characteristics of repetitive sequences of channel conformations. It turns out that the mitoBK channel activation by naringenin and quercetin does not lead to the change in the number of clusters within the phase space diagrams, which can be related to the constant number of available channel macroconformations regardless of the flavonoid administration. The localization and occupancy of the clusters of cross-correlated sequences suggest that mitoBK channel stimulation by flavonoids affects the relative stability of channel conformations and the kinetics of switching between them. For most clusters, greater net effects are observed in terms of quercetin administration in comparison with naringenin. It indicates stronger channel interaction with Que than Nar.

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“… 2021 , 2022 ; Richter-Laskowska et al. 2023 ). Quercetin, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one, is a flavonoid commonly found in various fruits, vegetables, and grains.…”

Section: Introductionmentioning

confidence: 99%

“… 2021 , 2022 ; Richter-Laskowska et al. 2023 ). Nevertheless, the molecular mechanisms of how these flavonoids can affect the conformational dynamics of the mitoBK channel are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

The cross-correlation-based analysis to digest the conformational dynamics of the mitoBK channels in terms of their modulation by flavonoids

Wawrzkiewicz-Jałowiecka

Trybek

Dworakowska

et al. 2023

Eur Biophys J

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“…Moreover, flavonoids can have a direct impact on ion channels. Various flavonoids act on potassium channels [17], and quercetin, a natural flavonoid, can activate the voltage-gated proton channel H V 1 [18].…”

Section: Introductionmentioning

confidence: 99%

A synthetic flavonoid derivate in the plasma membrane transforms the voltage‐clamp fluorometry signal of CiHv1

Pethő,

Pajtás,

Piga

et al. 2024

The FEBS Journal

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Voltage‐clamp fluorometry (VCF) enables the study of voltage‐sensitive proteins through fluorescent labeling accompanied by ionic current measurements for voltage‐gated ion channels. The heterogeneity of the fluorescent signal represents a significant challenge in VCF. The VCF signal depends on where the cysteine mutation is incorporated, making it difficult to compare data among different mutations and different studies and standardize their interpretation. We have recently shown that the VCF signal originates from quenching amino acids in the vicinity of the attached fluorophores, together with the effect of the lipid microenvironment. Based on these, we performed experiments to test the hypothesis that the VCF signal could be altered by amphiphilic quenching molecules in the cell membrane. Here we show that a phenylalanine‐conjugated flavonoid (4‐oxo‐2‐phenyl‐4H‐chromene‐7‐yl)‐phenylalanine, (later Oxophench) has potent effects on the VCF signals of the Ciona intestinalis HV1 (CiHv1) proton channel. Using spectrofluorimetry, we showed that Oxophench quenches TAMRA (5(6)‐carboxytetramethylrhodamine‐(methane thiosulfonate)) fluorescence. Moreover, Oxophench reduces the baseline fluorescence in oocytes and incorporates into the cell membrane while reducing the membrane fluidity of HEK293 cells. Our model calculations confirmed that Oxophench, a potent membrane‐bound quencher, modifies the VCF signal during conformational changes. These results support our previously published model of VCF signal generation and point out that a change in the VCF signal may not necessarily indicate an altered conformational transition of the investigated protein.

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Electrophysiology, molecular modelling, and functional analysis of the effects of dietary quercetin and flavonoid analogues on Kir6.1 channels in rat stomach fundus smooth muscle

Pettini,

Spiga,

Furini

et al. 2024

Biochemical Pharmacology

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Flavonoids as Modulators of Potassium Channels

Cited by 7 publications

References 221 publications

The cross-correlation-based analysis to digest the conformational dynamics of the mitoBK channels in terms of their modulation by flavonoids

The cross-correlation-based analysis to digest the conformational dynamics of the mitoBK channels in terms of their modulation by flavonoids

A synthetic flavonoid derivate in the plasma membrane transforms the voltage‐clamp fluorometry signal of CiHv1

Electrophysiology, molecular modelling, and functional analysis of the effects of dietary quercetin and flavonoid analogues on Kir6.1 channels in rat stomach fundus smooth muscle

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