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Alcohol metabolite acetic acid activates BK channels in a pH-dependent manner and decreases calcium oscillations and exocytosis of secretory granules in rat pituitary GH3 cells

  • Ion channels, receptors and transporters
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Abstract

Acetaldehyde and acetic acid/acetate, the active metabolites of alcohol (ethanol, EtOH), generate actions of their own ranging from behavioral, physiological, to pathological/cancerogenic effects. EtOH and acetaldehyde have been studied to some depth, whereas the effects of acetic acid have been less well explored. In this study, we investigated the effect of acetic acid on big conductance calcium-activated potassium (BK) channels present in GH3 rat pituitary tumor cells in more detail. In whole cell voltage clamp recordings, extracellular application of acetic acid increased total outward currents in a dose-dependent manner. This effect was prevented after the application of the specific BK channel blocker paxilline. Acetic acid action was pH-dependent—in whole cell current and single BK channel recordings, open probability (Po) was significantly increased by extracellular pH reduction and decreased by neutral or base pH. Acetic acid hyperpolarized the membrane potential, whereas acidic physiological solution had a depolarizing effect. Moreover, acetic acid reduced calcium (Ca2+) oscillations and exocytosis of growth hormone contained secretory granules from GH3 cells. These effects were partially prevented by BK inhibitors—tetraethylammonium or paxillin. In conclusion, our experiments indicate that acetic acid activates BK channels in GH3 cells which eventually contribute to acetic acid-induced membrane hyperpolarization, cessation of Ca2+ oscillations, and decrease of growth hormone release.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

Abbreviations

BK:

big-conductance calcium-activated potassium channels

AA:

acetic acid

EtOH:

ethanol

Po:

open probability

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Acknowledgments

We cordially thank Mag. Astrid Handlechner for her competent help in the cell culture lab.

Funding

Funded by Russian Foundation of Basic Research No. 19-315-90084 and the subsidy allocated to Kazan Federal University for the state assignment № 0671-2020-0059 in the sphere of scientific activities.

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Authors and Affiliations

  1. Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremlevskaya str. 18, Kazan, 420008, Russia

    Ilnar Shaidullov, Elizaveta Ermakova, Aleksey Yakovlev & Guzel Sitdikova

  2. Institute of Applied Physiology, University of Ulm, Ulm, Germany

    Aisylu Gaifullina

  3. Department of Neurophysiology and Neuropharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria

    Anna Mosshammer

  4. Department of Biosciences, University of Salzburg, Salzburg, Austria

    Thomas M. Weiger & Anton Hermann

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  1. Ilnar Shaidullov
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  2. Elizaveta Ermakova
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  3. Aisylu Gaifullina
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  4. Anna Mosshammer
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  5. Aleksey Yakovlev
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  6. Thomas M. Weiger
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  7. Anton Hermann
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  8. Guzel Sitdikova
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Contributions

I. Shaidullov: investigation, formal analysis. E.Ermakova: investigation, formal analysis, writing - original draft. A.Gaifullina: investigation, formal analysis. A. Mosshammer: investigation, formal analysis. A. Yakovlev: formal analysis, validation, visualization, writing - original draft. T.M. Weiger: conceptualization, methodology, writing - review and editing. A. Hermann: conceptualization, writing - original draft, writing - review and editing. G. Sitdikova: methodology, formal analysis, validation, visualization, writing - original draft, writing - review and editing, supervision, funding acquisition.

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Correspondence to Guzel Sitdikova.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

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Shaidullov, I., Ermakova, E., Gaifullina, A. et al. Alcohol metabolite acetic acid activates BK channels in a pH-dependent manner and decreases calcium oscillations and exocytosis of secretory granules in rat pituitary GH3 cells. Pflugers Arch - Eur J Physiol 473, 67–77 (2021). https://doi.org/10.1007/s00424-020-02484-0

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