Ca²⁺-mediated activation of the skeletal-muscle ryanodine receptor ion channel.

ABSTRACT: Cryo-electron micrograph studies recently have identified a Ca²⁺-binding site in the 2,200-kDa ryanodine receptor ion channel (RyR1) in skeletal muscle. To clarify the role of this site in regulating RyR1 activity, here we applied mutational, electrophysiological, and computational methods. Three amino acid residues that interact directly with Ca²⁺ were replaced, and these RyR1 variants were expressed in HEK293 cells. Single-site RyR1-E3893Q, -E3893V, -E3967Q, -E3967V, and -T5001A variants and double-site RyR1-E3893Q/E3967Q and -E3893V/E3967V variants displayed cellular Ca²⁺ release in response to caffeine, which indicated that they retained functionality as caffeine-sensitive, Ca²⁺-conducting channels in the HEK293 cell system. Using [³

SUBMITTER: Xu L 

PROVIDER: S-EPMC6302159 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature