Ryanodine receptor 1 mutations, dysregulation of calcium homeostasis and neuromuscular disorders.

The skeletal muscle ryanodine receptor is an intracellular calcium release channel which plays a central role in excitation contraction coupling. At least 80 mutations have been identified in the gene encoding the skeletal muscle ryanodine receptor and linked to several neuromuscular disorders, whose common feature appears to be a dysregulation of calcium homeostasis. A decade of research into the functional consequences of how these mutations affect the functional properties of the ryanodine receptor and their impact on disease, have significantly advanced our understanding of Malignant Hyperthermia, Central Core Disease and Multiminicore Disease. This review gives an overview of the important findings in the field of calcium homeostasis in skeletal muscle and describes how mutations in the ryanodine receptor gene might affect the function of this intracellular calcium release channel and lead to neuromuscular disorders.