Alcohol metabolite acetic acid activates BK channels in a pH-dependent manner and decreases calcium oscillations and exo
- PDF / 1,369,828 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 46 Downloads / 149 Views
ION CHANNELS, RECEPTORS AND TRANSPORTERS
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 Ilnar Shaidullov 1 & Elizaveta Ermakova 1 & Aisylu Gaifullina 2 & Anna Mosshammer 3 & Aleksey Yakovlev 1 & Thomas M. Weiger 4 & Anton Hermann 4 & Guzel Sitdikova 1 Received: 11 June 2020 / Revised: 16 October 2020 / Accepted: 20 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords : Acetic acid . Acetate . BK channels . pH dependence . Membrane potential . Ca2+ oscillations . Exocytosis
Introduction Metabolization of alcohol (ethanol, EtOH) involves in a first step enzymes such as alcohol dehydrogenase, cytochrome P450 (CYP450 2E1), or catalase to produce acetaldehyde. In a second step, acetaldehyde is quickly converted via aldehyde
* Guzel Sitdikova [email protected] 1
Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremlevskaya str. 18, Kazan 420008, Russia
2
Institute of Applied Physiology, University of Ulm, Ulm, Germany
3
Department of Neurophysiology and Neuropharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria
4
Department of Biosciences, University of Salzburg, Salzburg, Austria
dehydrogenase to more harmless acetic acid (AA) which in a third step is finally oxidized to carbon dioxide and water [18]. EtOH and its metabolites all appea
Data Loading...
