Effects of a domain peptide of the ryanodine receptor on Ca2+ release in skinned skeletal muscle fibers
Date
2001
Authors
Lamb, Graham D.
Posterino, Giuseppe Saverio
Yamamoto, Takeshi
Ikemoto, Noriaki
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
American Journal of Physiology-Cell Physiology, 2001; 281(1):c207-c214
Statement of Responsibility
Graham D. Lamb, Giuseppe S. Posterino, Takeshi Yamamoto, and Noriaki Ikemoto
Conference Name
Abstract
Mutations in the central domain of the skeletal muscle ryanodine receptor (RyR) cause malignant hyperthermia (MH). A synthetic peptide (DP4) in this domain (Leu-2442-Pro-2477) produces enhanced ryanodine binding and sensitized Ca2+ release in isolated sarcoplasmic reticulum, similar to the properties in MH, possibly because the peptide disrupts the normal interdomain interactions that stabilize the closed state of the RyR (Yamamoto T, El-Hayek R, and Ikemoto N. J Biol Chem 275: 11618-11625, 2000). Here, DP4 was applied to mechanically skinned fibers of rat muscle that had the normal excitation-contraction coupling mechanism still functional to determine whether muscle fiber responsiveness was enhanced. DP4 (100 µM) substantially potentiated the Ca2+ release and force response to caffeine (8 mM) and to low [Mg2+] (0.2 mM) in every fiber examined, with no significant effect on the properties of the contractile apparatus. DP4 also potentiated the response to submaximal depolarization of the transverse tubular system by ionic substitution. Importantly, DP4 did not significantly alter the size of the twitch response elicited by action potential stimulation. These results support the proposal that DP4 causes an MH-like aberration in RyR function and are consistent with the voltage sensor triggering Ca2+ release by destabilizing the closed state of the RyRs.
School/Discipline
School of Molecular and Biomedical Science
Dissertation Note
Provenance
Description
Published abstract reprinted by permission
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© 2001 American Physiological Society