A central core disease mutation in the Ca²⁺-binding site of skeletal muscle ryanodine receptor impairs single-channel regulation.

ABSTRACT: Cryoelectron microscopy and mutational analyses have shown that type 1 ryanodine receptor (RyR1) amino acid residues RyR1-E3893, -E3967, and -T5001 are critical for Ca²⁺-mediated activation of skeletal muscle Ca²⁺ release channel. De novo missense mutation RyR1-Q3970K in the secondary binding sphere of Ca²⁺ was reported in association with central core disease (CCD) in a 2-yr-old boy. Here, we characterized recombinant RyR1-Q3970K mutant by cellular Ca²⁺ release measurements, single-channel recordings, and computational methods. Caffeine-induced Ca²⁺ release studies indicated that RyR1-Q3970K formed caffeine-sensitive, Ca²⁺-conducting channel in HEK293 cells. However, in single-channel recordings, RyR1-Q3970K displayed low C

SUBMITTER: Chirasani VR 

PROVIDER: S-EPMC6732417 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature