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.

journal_name

Ann N Y Acad Sci

authors

MacLennan DH,Chen SR

doi

10.1111/j.1749-6632.1993.tb38060.x

subject

Has Abstract

pub_date

1993-12-20 00:00:00

pages

294-304

eissn

0077-8923

issn

1749-6632

journal_volume

707

pub_type

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