The role of the calcium release channel of skeletal muscle sarcoplasmic reticulum in malignant hyperthermia

Abstract

In this short review, we have described studies that have identified Arg415 in the Ca2+ release channel as a residue that influences channel sensitivity to Ca2+ induced Ca2+ release, rate of Ca2+ release, and channel closing. We have also described studies that confirm Dr. Numa's predictions that residues 4246-4267, 4382-4417, and 4478-4512 contain Ca2+ binding sites. The site between residues 4483 and 4494 (the PE repeat sequence) may be a key binding site for Ca2+ activation of the channel. Other residues in the sequence 4478-4512 may also contribute to activation of the channel. Thus our studies have contributed to basic knowledge of regulation of Ca2+ release function. They have also provided practical benefits in defining a disease gene, in development of a diagnostic test for porcine MH that is of economic benefit, and in laying the foundation for human MH diagnostic tests that may prevent anesthesia-induced morbidity and mortality.