Dallas, ML, Peers, C, Golder, FJ et al. (3 more authors) (2015) GAL-021 and GAL-160 are Efficacious in Rat Models of Obstructive and Central Sleep Apnea and Inhibit BKCa in Isolated Rat Carotid Body Glomus Cells. In: Arterial Chemoreceptors in Physiology and Pathophysiology. Advances in Experimental Medicine and Biology, 860 . Springer International Publishing , pp. 361-370. ISBN 978-3-319-18439-5
Abstract
GAL-021 and GAL-160 are alkylamino triazine analogues, which stimulate ventilation in rodents, non-human primates and (for GAL-021) in humans. To probe the site and mechanism of action of GAL-021 and GAL-160 we utilized spirometry in urethane anesthetized rats subjected to acute bilateral carotid sinus nerve transection (CSNTX) or sham surgery. In addition, using patch clamp electrophysiology we evaluated ionic currents in carotid body glomus cells isolated from neonatal rats. Acute CSNTX markedly attenuated and in some instances abolished the ventilatory stimulant effects of GAL-021 and GAL-160 (0.3 mg/kg IV), suggesting the carotid body is a/the major locus of action. Electrophysiology studies, in isolated Type I cells, established that GAL-021 (30 μM) and GAL-160 (30 μM) inhibited the BKCa current without affecting the delayed rectifier K+, leak K+ or inward Ca2+ currents. At a higher concentration of GAL-160 (100 μM), inhibition of the delayed rectifier K+ current and leak K+ current were observed. These data are consistent with the concept that GAL-021 and GAL-160 influence breathing control by acting as peripheral chemoreceptor modulators predominantly by inhibiting BKCa mediated currents in glomus cells of the carotid body.
Metadata
Item Type: | Book Section |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) Springer International Publishing Switzerland 2015. This is an author produced version of a chapter published in Arterial Chemoreceptors in Physiology and Pathophysiology, Advances in Experimental Medicine and Biology Volume 860. Editors: Chris Peers, Prem Kumar, Christopher Wyatt, Estelle Gauda, Colin A. Nurse, Nanduri Prabhakar. http://dx.doi.org/10.1007/978-3-319-18440-1 |
Keywords: | GAL-021; GAL-160; BKCa channel; Carotid body; Carotid sinus nerve; Peripheral chemoreceptor modulators |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Genetics, Health and Therapeutics (LIGHT) > Academic Unit of Cardiovascular Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 Jun 2016 15:01 |
Last Modified: | 15 Jan 2018 21:05 |
Published Version: | http://dx.doi.org/10.1007/978-3-319-18440-1_41 |
Status: | Published |
Publisher: | Springer International Publishing |
Series Name: | Advances in Experimental Medicine and Biology |
Identification Number: | 10.1007/978-3-319-18440-1_41 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:98725 |