{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:45:54Z","timestamp":1790214354496,"version":"4.1.0"},"reference-count":0,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1991,8,1]]},"abstract":"<jats:p> The binding properties of [3H]ryanodine, a specific ligand of the receptor complex that forms the Ca2+ release channel of sarcoplasmic reticulum, were studied in normal (N) and malignant hyperthermia-susceptible (MH) human skeletal muscle. Integrity of the solubilized ryanodine receptor was demonstrated by single-channel recordings in planar bilayers and by the changes produced by activators and inhibitors of the Ca2+ release channel on the binding properties of [3H]ryanodine. N and MH receptors were capable of binding [3H]ryanodine in a Ca(2+)-dependent manner. Scatchard analysis showed that a single binding site for [3H]ryanodine was present in either N or MH muscle. Binding affinity was approximately the same in N and MH (Kd approximately 7 nM), when the Ca2+ concentration was greater than 30 microM. At 0.3 microM Ca2+, MH receptors displayed a higher affinity for [3H]ryanodine (Kd = 4.1 +\/- 1.0 nM) than N receptors (Kd = 7.1 +\/- 0.8 nM). The presence of a single Kd for [3H]ryanodine in MH muscle, distinct from that of N muscle, indicated that MH muscle does not have detectable levels of N receptors. Ca2+ dependence of [3H]ryanodine binding further suggested that MH receptors had a higher affinity for Ca2+ (Kd[Ca2+] = 120 +\/- 50 nM) than N receptors (Kd[Ca2+] = 250 +\/- 80 nM). Caffeine increased [3H]ryanodine binding at submicromolar [Ca2+], and the effect was larger in MH. Apparent affinity constants for caffeine were 13 +\/- 1.8 mM in N and 6 +\/- 0.8 mM in MH receptors. Evidently, the ryanodine receptor of MH-susceptible human skeletal muscle has an unusually high sensitivity to Ca2+ which is augmented by caffeine.(ABSTRACT TRUNCATED AT 250 WORDS) <\/jats:p>","DOI":"10.1152\/ajpcell.1991.261.2.c237","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T13:33:10Z","timestamp":1514122390000},"page":"C237-C245","source":"Crossref","is-referenced-by-count":37,"title":["Altered binding site for Ca2+ in the ryanodine receptor of human malignant hyperthermia"],"prefix":"10.1152","volume":"261","author":[{"given":"H. H.","family":"Valdivia","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Wisconsin Medical School,Madison 53706."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Hogan","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Wisconsin Medical School,Madison 53706."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Coronado","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Wisconsin Medical School,Madison 53706."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.1991.261.2.C237","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T19:46:08Z","timestamp":1718653568000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.1991.261.2.C237"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,8,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1991,8,1]]}},"alternative-id":["10.1152\/ajpcell.1991.261.2.C237"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.1991.261.2.c237","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[1991,8,1]]}}}