학술논문
Hydrocortisone inhibition of wild-type and αD200Q nicotinic acetylcholine receptors.
Document Type
Academic Journal
Author
Dworakowska B; Department of Biophysics, Warsaw University of Life Sciences-SGGW, Warsaw, Poland.; Nurowska E; Laboratory of Physiology and Pathophysiology, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Warsaw, Poland.; Dołowy K; Department of Biophysics, Warsaw University of Life Sciences-SGGW, Warsaw, Poland.
Source
Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101262549 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1747-0285 (Electronic) Linking ISSN: 17470277 NLM ISO Abbreviation: Chem Biol Drug Des
Subject
Language
English
Abstract
Short-term treatment with large doses of corticosteroids can result in acute weakness of muscles in processes that have not yet been fully characterized. Corticosteroids have been shown to exert direct inhibitory action on the muscle-type nicotinic acetylcholine receptor (AChR), and therefore can promote pharmacological muscle denervation. The mechanism of hydrocortisone (HC) blockage of AChR has not been fully established yet. It is uncommon for an electrically neutral molecule, for example, HC, to induce voltage-dependent changes in AChR kinetics. Our experiments aimed to determine the source of voltage-dependency in HC action. Wild-type (WT) and αD200Q receptors were transiently expressed in HEK293 cells. Recordings were performed in either the presence or absence of HC. We showed that the D-to-Q substitution is capable of suppressing the voltage dependency in the HC-induced block. We conclude that the distance between αD200 and the agonist-binding site depends on the membrane potential. The voltage-dependent changes of the αD200 position have not been considered yet. To our knowledge, the ability to induce voltage-dependency in blocker action has not been shown previously for an amino acid located outside the transmembrane portion of the receptor. Possible mechanisms of HC block (allosteric and knocking) in WT and αD200Q receptors are discussed.
(© 2018 John Wiley & Sons A/S.)
(© 2018 John Wiley & Sons A/S.)