Document Type
Article
Source of Publication
Frontiers in Pharmacology
Publication Date
12-18-2020
Abstract
© Copyright © 2020 Melnyk, Dryn, Kury, Dziuba and Zholos. A better understanding of the negative impact of general anesthetics on gastrointestinal motility requires thorough knowledge of their molecular targets. In this respect the muscarinic cationic current (mICAT carried mainly via TRPC4 channels) that initiates cholinergic excitation-contraction coupling in the gut is of special interest. Here we aimed to characterize the effects of one of the most commonly used “dissociative anesthetics”, ketamine, on mICAT. Patch-clamp and tensiometry techniques were used to investigate the mechanisms of the inhibitory effects of ketamine on mICAT in single mouse ileal myocytes, as well as on intestinal motility. Ketamine (100 µM) strongly inhibited both carbachol- and GTPγS-induced mICAT. The inhibition was slow (time constant of about 1 min) and practically irreversible. It was associated with altered voltage dependence and kinetics of mICAT. In functional tests, ketamine suppressed both spontaneous and carbachol-induced contractions of small intestine. Importantly, inhibited by ketamine mICAT could be restored by direct TRPC4 agonist (-)-englerin A. We identified mICAT as a novel target for ketamine. Signal transduction leading to TRPC4 channel opening is disrupted by ketamine mainly downstream of muscarinic receptor activation, but does not involve TRPC4 per se. Direct TRPC4 agonists may be used for the correction of gastrointestinal disorders provoked by general anesthesia.
DOI Link
ISSN
Publisher
Frontiers Media SA
Volume
11
First Page
594882
Disciplines
Medicine and Health Sciences
Keywords
(-)-englerin A, G-proteins, gastrointestinal tract, ketamine, postoperative ileus, transient receptor potential canonical subfamily member 4 channel
Scopus ID
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Melnyk, Mariia I.; Dryn, Dariia O.; Al Kury, Lina T.; Dziuba, Dmytro O.; and Zholos, Alexander V., "Suppression of mICAT in Mouse Small Intestinal Myocytes by General Anaesthetic Ketamine and its Recovery by TRPC4 Agonist (-)-englerin A" (2020). All Works. 3260.
https://zuscholars.zu.ac.ae/works/3260
Indexed in Scopus
yes
Open Access
yes
Open Access Type
Gold: This publication is openly available in an open access journal/series