Ryanodinopathies: RyR-Linked Muscle Diseases.

摘要: Publisher Summary This chapter examines the clinical characteristics, genetics, and pathophysiological mechanisms of ryanodinopathies, an eclectic array clinically distinct muscle disorders caused by inherited acquired alterations in skeletal cardiac ryanodine receptor (RyR) function. Ryanodinopathies results from mutations functional skeletal—RyR1—and cardiac—RyR2—muscle RyRs. RyR1 are linked to malignant hyperthermia (MH), a hypermetabolic pharmacogenetic disorder triggered volatile anesthetics several congenital myopathies, including central core disease (CCD), multi-minicore disease, core-rod myopathy, centronuclear myopathy. The discusses potential mechanism which RyR alter channel sensitivity, leak, release: (1) hyperphosphorylation FK506 binding protein (FKBP) dissociation, (2) disruption critical interdomain regulatory interactions, (3) enhanced store overload-induced Ca 2+ release, (4) reduced RyR-mediated flux because altered gating or permeation.