KCNQ and KCNE Isoform-Dependent Pharmacology Rationalizes Native American Dual Use of Specific Plants as Both Analgesics and Gastrointestinal Therapeutics.

Autor:	Abbott GW; Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA, United States., Redford KE; Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA, United States., Yoshimura RF; Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA, United States., Manville RW; Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA, United States., Moreira L; Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA, United States., Tran K; Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA, United States., Arena G; Redwood Creek Vegetation Team, National Park Service, Sausalito, CA, United States., Kookootsedes A; Redwood Creek Vegetation Team, National Park Service, Sausalito, CA, United States., Lasky E; Redwood Creek Vegetation Team, National Park Service, Sausalito, CA, United States., Gunnison E; Redwood Creek Vegetation Team, National Park Service, Sausalito, CA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in physiology [Front Physiol] 2021 Nov 11; Vol. 12, pp. 777057. Date of Electronic Publication: 2021 Nov 11 (Print Publication: 2021).
DOI:	10.3389/fphys.2021.777057
Abstrakt:	Indigenous peoples of the Americas are proficient in botanical medicine. KCNQ family voltage-gated potassium (Kv) channels are sensitive to a variety of ligands, including plant metabolites. Here, we screened methanolic extracts prepared from 40 Californian coastal redwood forest plants for effects on Kv current and membrane potential in Xenopus oocytes heterologously expressing KCNQ2/3, which regulates excitability of neurons, including those that sense pain. Extracts from 9 of the 40 plant species increased KCNQ2/3 current at -60 mV by ≥threefold (maximally, 15-fold by Urtica dioica ) and/or hyperpolarized membrane potential by ≥-3 mV (maximally, -11 mV by Arctostaphylos glandulosa ). All nine plants have traditionally been used as both analgesics and gastrointestinal therapeutics. Of two extracts tested, both acted as KCNQ-dependent analgesics in mice. KCNQ2/3 activation at physiologically relevant, subthreshold membrane potentials by tannic acid, gallic acid and quercetin provided molecular correlates for analgesic action of several of the plants. While tannic acid also activated KCNQ1 and KCNQ1-KCNE1 at hyperpolarized, negative membrane potentials, it inhibited KCNQ1-KCNE3 at both negative and positive membrane potentials, mechanistically rationalizing historical use of tannic acid-containing plants as gastrointestinal therapeutics. KCNE dependence of KCNQ channel modulation by plant metabolites therefore provides a molecular mechanistic basis for Native American use of specific plants as both analgesics and gastrointestinal aids. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Abbott, Redford, Yoshimura, Manville, Moreira, Tran, Arena, Kookootsedes, Lasky and Gunnison.)
Databáze:	MEDLINE
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