{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T22:23:29Z","timestamp":1758925409450},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1996,4,15]]},"abstract":"<jats:p>1. Propranolol, a \u03b2-blocker, inhibited or stimulated ryanodine binding to both the membrane-bound and purified ryanodine receptor (RyR) depending on the assay conditions. At high NaCl concentrations, propranolol increased the number of ryanodine-binding sites (Bmax) with no effect on the binding affinity. In the presence of 0.2 M NaCl, ryanodine binding was inhibited by propranolol. Half-maximal inhibition was obtained at 1.2 mM and complete inhibition at 2 mM propranolol. The inhibitory effect of propranolol obtained at low NaCl concentration was not restored by increasing the NaCl concentration to 1 M. 2. Modulators of the RyR that are known to alter its conformational states, such as adenine nucleotides, Ca2+ concentration and pH, modified the effect of propranolol on ryanodine binding. In the presence of propranolol and at low NaCl concentrations, ryanodine binding was inhibited and showed no Ca2+-, pH- or time-dependence. 3. Propranolol immediately and completely blocked the channel opening of RyR reconstituted into a planar lipid bilayer. Propranolol-modified non-active channel was reactivated to a subconductive state (about 40% of the control conductance) by ATP. 4. Competition experiments between lidocaine (a stimulatory drug) or tetracaine (an inhibitory drug) and propranolol at 0.2 or 1.0 M NaCl, respectively, suggest the existence of different interaction sites for local anaesthetics and propranolol. 5. These results suggest that propranolol interacts directly with the RyR and modifies its ryanodine binding and single-channel activities. Propranolol effects are altered by the RyR conformational state, suggesting its possible use as a conformational probe for RyR.<\/jats:p>","DOI":"10.1042\/bj3150377","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:48:38Z","timestamp":1439243318000},"page":"377-383","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Ryanodine receptor\/calcium release channel conformations as reflected in the different effects of propranolol on its ryanodine binding and channel activity"],"prefix":"10.1042","volume":"315","author":[{"given":"Sigalit","family":"ZCHUT","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"FENG","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varda","family":"SHOSHAN-BARMATZ","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/315\/2\/377\/619808\/bj3150377.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/315\/2\/377\/619808\/bj3150377.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:14:55Z","timestamp":1637712895000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/315\/2\/377\/32899\/Ryanodine-receptor-calcium-release-channel"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,4,15]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1996,4,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj3150377","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,4,15]]}}}