{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T20:01:40Z","timestamp":1762113700098},"reference-count":43,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2001,7,1]]},"abstract":"<jats:p> 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\u2013Pro-2477) produces enhanced ryanodine binding and sensitized Ca<jats:sup>2+<\/jats:sup> 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\u201311625, 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 \u03bcM) substantially potentiated the Ca<jats:sup>2+<\/jats:sup>release and force response to caffeine (8 mM) and to low [Mg<jats:sup>2+<\/jats:sup>] (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 Ca<jats:sup>2+<\/jats:sup> release by destabilizing the closed state of the RyRs. <\/jats:p>","DOI":"10.1152\/ajpcell.2001.281.1.c207","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T20:05:28Z","timestamp":1514145928000},"page":"C207-C214","source":"Crossref","is-referenced-by-count":32,"title":["Effects of a domain peptide of the ryanodine receptor on Ca<sup>2+<\/sup> release in skinned skeletal muscle fibers"],"prefix":"10.1152","volume":"281","author":[{"given":"Graham D.","family":"Lamb","sequence":"first","affiliation":[{"name":"Department of Zoology, La Trobe University, Bundoora, Victoria 3086, Australia; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe S.","family":"Posterino","sequence":"additional","affiliation":[{"name":"Department of Zoology, La Trobe University, 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