We have located links that may give you full text access.
Malignant hyperthermia-associated mutations in the S2-S3 cytoplasmic loop of type 1 ryanodine receptor calcium channel impair calcium-dependent inactivation.
American Journal of Physiology. Cell Physiology 2016 November 2
Channel activities of skeletal muscle ryanodine receptor (RyR1) are activated by micromolar Ca(2+) and inactivated by higher (∼1 mM) Ca(2+) To gain insight into a mechanism underlying Ca(2+)-dependent inactivation of RyR1 and its relationship with skeletal muscle diseases, we constructed nine recombinant RyR1 mutants carrying malignant hyperthermia or centronuclear myopathy-associated mutations and determined RyR1 channel activities by [(3)H]ryanodine binding assay. These mutations are localized in or near the RyR1 domains which are responsible for Ca(2+)-dependent inactivation of RyR1. Four RyR1 mutations (F4732D, G4733E, R4736W, and R4736Q) in the cytoplasmic loop between the S2 and S3 transmembrane segments (S2-S3 loop) greatly reduced Ca(2+)-dependent channel inactivation. Activities of these mutant channels were suppressed at 10-100 μM Ca(2+), and the suppressions were relieved by 1 mM Mg(2+) The Ca(2+)- and Mg(2+)-dependent regulation of S2-S3 loop RyR1 mutants are similar to those of the cardiac isoform of RyR (RyR2) rather than wild-type RyR1. Two mutations (T4825I and H4832Y) in the S4-S5 cytoplasmic loop increased Ca(2+) affinities for channel activation and decreased Ca(2+) affinities for inactivation, but impairment of Ca(2+)-dependent inactivation was not as prominent as those of S2-S3 loop mutants. Three mutations (T4082M, S4113L, and N4120Y) in the EF-hand domain showed essentially the same Ca(2+)-dependent channel regulation as that of wild-type RyR1. The results suggest that nine RyR1 mutants associated with skeletal muscle diseases were differently regulated by Ca(2+) and Mg(2+) Four malignant hyperthermia-associated RyR1 mutations in the S2-S3 loop conferred RyR2-type Ca(2+)- and Mg(2+)-dependent channel regulation.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app