An alkaloid from the South American shrub Ryania speciosa that blocks calcium release from the sarcoplasmic reticulum of skeletal muscle. The ryanodine receptor is a large transmembrane protein with skeletal muscle (RyR1, 5032 aa), cardiac muscle (RyR2, 4965 aa) and brain (RyR3, 4872 aa) isoforms. The cardiac channel is a tetramer comprised of four RYR2 polypeptides and four calstabin (FK506-binding protein 1B) subunits and is opened by PKA-mediated phosphorylation; the other channels are similar. The ryanodine-receptor channels exhibit a positive feedback in which increased intracellular calcium triggers opening and gives a very rapid response. RyR1 mutations are associated with malignant hyperthermia and central core disease, RyR2 mutations with stress-induced ventricular tachycardia. RYR3 is thought to have a role in hippocampal synaptic plasticity, particularly the modification of acquired memory in response to external stimuli.
Subjects: Medicine and Health.