{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T11:40:03Z","timestamp":1739965203710,"version":"3.37.3"},"reference-count":42,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["molpharm.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Pharmacology"],"published-print":{"date-parts":[[2014,9]]},"DOI":"10.1124\/mol.114.093757","type":"journal-article","created":{"date-parts":[[2014,7,8]],"date-time":"2014-07-08T01:10:32Z","timestamp":1404781832000},"page":"318-329","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"title":["Insights into the Gating Mechanism of the Ryanodine-Modified Human Cardiac Ca2+-Release Channel (Ryanodine Receptor 2)"],"prefix":"10.1016","volume":"86","author":[{"given":"Saptarshi","family":"Mukherjee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. Lowri","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan J.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1124\/mol.114.093757_bib1","doi-asserted-by":"crossref","first-page":"5456","DOI":"10.1111\/febs.12194","article-title":"Ryanodine receptor calcium release channels: lessons from structure-function studies","volume":"280","author":"Amador","year":"2013","journal-title":"FEBS J"},{"key":"10.1124\/mol.114.093757_bib2","doi-asserted-by":"crossref","first-page":"C144","DOI":"10.1152\/ajpcell.1996.271.1.C144","article-title":"Modal gating in neuronal and skeletal muscle ryanodine-sensitive Ca2+ release channels","volume":"271","author":"Armis\u00e9n","year":"1996","journal-title":"Am J Physiol"},{"key":"10.1124\/mol.114.093757_bib3","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1085\/jgp.200709898","article-title":"How to turn the reaction coordinate into time","volume":"130","author":"Auerbach","year":"2007","journal-title":"J Gen Physiol"},{"key":"10.1124\/mol.114.093757_bib4","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/415198a","article-title":"Cardiac excitation-contraction coupling","volume":"415","author":"Bers","year":"2002","journal-title":"Nature"},{"key":"10.1124\/mol.114.093757_bib5","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nrm2376","article-title":"How membrane proteins sense voltage","volume":"9","author":"Bezanilla","year":"2008","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1124\/mol.114.093757_bib6","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.neuron.2010.08.021","article-title":"Ion channel voltage sensors: structure, function, and pathophysiology","volume":"67","author":"Catterall","year":"2010","journal-title":"Neuron"},{"key":"10.1124\/mol.114.093757_bib7","doi-asserted-by":"crossref","first-page":"e26693","DOI":"10.1371\/journal.pone.0026693","article-title":"Modulation of cardiac ryanodine receptor channels by alkaline earth cations","volume":"6","author":"Diaz-Sylvester","year":"2011","journal-title":"PLoS One"},{"key":"10.1124\/mol.114.093757_bib8","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1126\/science.280.5360.69","article-title":"The structure of the potassium channel: molecular basis of K+ conduction and selectivity","volume":"280","author":"Doyle","year":"1998","journal-title":"Science"},{"key":"10.1124\/mol.114.093757_bib9","doi-asserted-by":"crossref","first-page":"13625","DOI":"10.1073\/pnas.241516898","article-title":"Ryanodine sensitizes the cardiac Ca(2+) release channel (ryanodine receptor isoform 2) to Ca(2+) activation and dissociates as the channel is closed by Ca(2+) depletion","volume":"98","author":"Du","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/mol.114.093757_bib10","doi-asserted-by":"crossref","first-page":"7256","DOI":"10.1073\/pnas.82.21.7256","article-title":"Localization of Ca2+ release channels with ryanodine in junctional terminal cisternae of sarcoplasmic reticulum of fast skeletal muscle","volume":"82","author":"Fleischer","year":"1985","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/mol.114.093757_bib11","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1023\/A:1019935832427","article-title":"Linear free-energy relationships and the dynamics of gating in the acetylcholine receptor channel","volume":"28","author":"Grosman","year":"2002","journal-title":"J Biol Phys"},{"key":"10.1124\/mol.114.093757_bib12","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.pharmthera.2008.06.002","article-title":"Dysregulated sarcoplasmic reticulum calcium release: potential pharmacological target in cardiac disease","volume":"119","author":"Gy\u00f6rke","year":"2008","journal-title":"Pharmacol Ther"},{"year":"2001","author":"Hille","series-title":"Ion Channels of Excitable Membranes","key":"10.1124\/mol.114.093757_bib13"},{"key":"10.1124\/mol.114.093757_bib14","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/ps.3406","article-title":"The story of a new insecticidal chemistry class: the diamides","volume":"69","author":"Jeanguenat","year":"2013","journal-title":"Pest Manag Sci"},{"key":"10.1124\/mol.114.093757_bib15","doi-asserted-by":"crossref","first-page":"a003996","DOI":"10.1101\/cshperspect.a003996","article-title":"Ryanodine receptors: structure, expression, molecular details, and function in calcium release","volume":"2","author":"Lanner","year":"2010","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"10.1124\/mol.114.093757_bib16","doi-asserted-by":"crossref","first-page":"3541","DOI":"10.1529\/biophysj.106.099028","article-title":"Ca2+ stores regulate ryanodine receptor Ca2+ release channels via luminal and cytosolic Ca2+ sites","volume":"92","author":"Laver","year":"2007","journal-title":"Biophys J"},{"key":"10.1124\/mol.114.093757_bib17","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1016\/S0006-3495(98)77944-5","article-title":"Inactivation of Ca2+ release channels (ryanodine receptors RyR1 and RyR2) with rapid steps in [Ca2+] and voltage","volume":"74","author":"Laver","year":"1998","journal-title":"Biophys J"},{"key":"10.1124\/mol.114.093757_bib18","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1085\/jgp.104.3.425","article-title":"How does ryanodine modify ion handling in the sheep cardiac sarcoplasmic reticulum Ca(2+)-release channel?","volume":"104","author":"Lindsay","year":"1994","journal-title":"J Gen Physiol"},{"key":"10.1124\/mol.114.093757_bib19","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1085\/jgp.201210851","article-title":"The contribution of hydrophobic residues in the pore-forming region of the ryanodine receptor channel to block by large tetraalkylammonium cations and Shaker B inactivation peptides","volume":"140","author":"Mason","year":"2012","journal-title":"J Gen Physiol"},{"key":"10.1124\/mol.114.093757_bib20","doi-asserted-by":"crossref","first-page":"39727","DOI":"10.1074\/jbc.M106557200","article-title":"Ryanodine sensitizes the Ca(2+) release channel (ryanodine receptor) to Ca(2+) activation","volume":"276","author":"Masumiya","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1124\/mol.114.093757_bib21","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/aps.2011.44","article-title":"Targeting ryanodine receptors for anti-arrhythmic therapy","volume":"32","author":"McCauley","year":"2011","journal-title":"Acta Pharmacol Sin"},{"key":"10.1124\/mol.114.093757_bib22","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1016\/S0006-3495(02)75545-8","article-title":"Ryanodine-induced structural alterations in the RyR channel suggested by neomycin block","volume":"82","author":"Mead","year":"2002","journal-title":"Biophys J"},{"key":"10.1124\/mol.114.093757_bib23","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1085\/jgp.201110706","article-title":"A mechanistic description of gating of the human cardiac ryanodine receptor in a regulated minimal environment","volume":"140","author":"Mukherjee","year":"2012","journal-title":"J Gen Physiol"},{"key":"10.1124\/mol.114.093757_bib24","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.toxicon.2013.07.012","article-title":"Scorpion venom components that affect ion-channels function","volume":"76","author":"Quintero-Hern\u00e1ndez","year":"2013","journal-title":"Toxicon"},{"key":"10.1124\/mol.114.093757_bib25","doi-asserted-by":"crossref","first-page":"6154","DOI":"10.1074\/jbc.M112.433789","article-title":"Structural determinants of skeletal muscle ryanodine receptor gating","volume":"288","author":"Ramachandran","year":"2013","journal-title":"J Biol Chem"},{"key":"10.1124\/mol.114.093757_bib26","doi-asserted-by":"crossref","first-page":"3086","DOI":"10.1021\/ja01189a074","article-title":"Plant insecticides; ryanodine, a new alkaloid from Ryania speciosa Vahl","volume":"70","author":"Rogers","year":"1948","journal-title":"J Am Chem Soc"},{"key":"10.1124\/mol.114.093757_bib27","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1146\/annurev.biophys.34.040204.144655","article-title":"Ion conduction and selectivity in K(+) channels","volume":"34","author":"Roux","year":"2005","journal-title":"Annu Rev Biophys Biomol Struct"},{"key":"10.1124\/mol.114.093757_bib28","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/j.1476-5381.2009.00147.x","article-title":"Characterization of hadrucalcin, a peptide from Hadrurus gertschi scorpion venom with pharmacological activity on ryanodine receptors","volume":"157","author":"Schwartz","year":"2009","journal-title":"Br J Pharmacol"},{"key":"10.1124\/mol.114.093757_bib29","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/BF00232590","article-title":"Regulation of the gating of the sheep cardiac sarcoplasmic reticulum Ca(2+)-release channel by luminal Ca2+","volume":"137","author":"Sitsapesan","year":"1994","journal-title":"J Membr Biol"},{"key":"10.1124\/mol.114.093757_bib30","doi-asserted-by":"crossref","first-page":"C1235","DOI":"10.1152\/ajpcell.1995.268.5.C1235","article-title":"Cyclic ADP-ribose and related compounds activate sheep skeletal sarcoplasmic reticulum Ca2+ release channel","volume":"268","author":"Sitsapesan","year":"1995","journal-title":"Am J Physiol"},{"key":"10.1124\/mol.114.093757_bib31","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s00232-008-9102-z","article-title":"Single-channel characterization of the rabbit recombinant RyR2 reveals a novel inactivation property of physiological concentrations of ATP","volume":"222","author":"Stewart","year":"2008","journal-title":"J Membr Biol"},{"key":"10.1124\/mol.114.093757_bib32","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.cardiores.2004.06.009","article-title":"Functional heterogeneity of ryanodine receptor mutations associated with sudden cardiac death","volume":"64","author":"Thomas","year":"2004","journal-title":"Cardiovasc Res"},{"key":"10.1124\/mol.114.093757_bib33","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1016\/S0006-3495(93)81201-3","article-title":"Using large organic cations to probe the nature of ryanodine modification in the sheep cardiac sarcoplasmic reticulum calcium release channel","volume":"65","author":"Tinker","year":"1993","journal-title":"Biophys J"},{"key":"10.1124\/mol.114.093757_bib34","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1085\/jgp.111.5.679","article-title":"Imperatoxin A induces subconductance states in Ca2+ release channels (ryanodine receptors) of cardiac and skeletal muscle","volume":"111","author":"Tripathy","year":"1998","journal-title":"J Gen Physiol"},{"key":"10.1124\/mol.114.093757_bib35","doi-asserted-by":"crossref","first-page":"31624","DOI":"10.1074\/jbc.R112.349068","article-title":"Ryanodine receptors: structure and function","volume":"287","author":"Van Petegem","year":"2012","journal-title":"J Biol Chem"},{"key":"10.1124\/mol.114.093757_bib36","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nrcardio.2012.93","article-title":"Inherited calcium channelopathies in the pathophysiology of arrhythmias","volume":"9","author":"Venetucci","year":"2012","journal-title":"Nat Rev Cardiol"},{"key":"10.1124\/mol.114.093757_bib37","doi-asserted-by":"crossref","first-page":"d1727","DOI":"10.2741\/A876","article-title":"Quantitative relationships between ryanoids, receptor affinity and channel conductance","volume":"7","author":"Welch","year":"2002","journal-title":"Front Biosci"},{"key":"10.1124\/mol.114.093757_bib38","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1529\/biophysj.104.044180","article-title":"A model of the putative pore region of the cardiac ryanodine receptor channel","volume":"87","author":"Welch","year":"2004","journal-title":"Biophys J"},{"key":"10.1124\/mol.114.093757_bib39","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.1021\/bi9623901","article-title":"Structural components of ryanodine responsible for modulation of sarcoplasmic reticulum calcium channel function","volume":"36","author":"Welch","year":"1997","journal-title":"Biochemistry"},{"key":"10.1124\/mol.114.093757_bib40","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1017\/S0033583501003675","article-title":"Light at the end of the Ca(2+)-release channel tunnel: structures and mechanisms involved in ion translocation in ryanodine receptor channels","volume":"34","author":"Williams","year":"2001","journal-title":"Q Rev Biophys"},{"key":"10.1124\/mol.114.093757_bib41","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1016\/S0006-3495(95)80048-2","article-title":"Description of modal gating of the cardiac calcium release channel in planar lipid membranes","volume":"69","author":"Zahradn\u00edkov\u00e1","year":"1995","journal-title":"Biophys J"},{"key":"10.1124\/mol.114.093757_bib42","doi-asserted-by":"crossref","first-page":"3680","DOI":"10.1529\/biophysj.105.067215","article-title":"Phi-value analysis of a linear, sequential reaction mechanism: theory and application to ion channel gating","volume":"89","author":"Zhou","year":"2005","journal-title":"Biophys J"}],"container-title":["Molecular Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24039750?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24039750?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/mol.114.093757","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T11:22:33Z","timestamp":1739964153000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0026895X24039750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,9]]}},"alternative-id":["S0026895X24039750"],"URL":"https:\/\/doi.org\/10.1124\/mol.114.093757","relation":{},"ISSN":["0026-895X"],"issn-type":[{"type":"print","value":"0026-895X"}],"subject":[],"published":{"date-parts":[[2014,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Insights into the Gating Mechanism of the Ryanodine-Modified Human Cardiac Ca2+-Release Channel (Ryanodine Receptor 2)","name":"articletitle","label":"Article Title"},{"value":"Molecular Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/mol.114.093757","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2014 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}