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28687594,18505726,27586648,15347586,27623776,17259277,12124989,11524458,10790202,23746327,26115329,12642598,9334205,27558158,16239587,11063719,27733687,15322274,10484775,28961276,26663082,9873004,28527222,15689621,16917943,25605235,15336973,18092949,16075044,19541610,15336975,16732084,20676041,21926372,16958053,17182726,20944434,11278295,11741831,35867837,18313359,23498838,27154203,15336972,15589992,26309258,28807150,21825032,11807805,25958340,19460614,24805197,36082968,21291389,26584883,17081152,31166712,28584051,25998124,27382027,27013634,18305228,10888602,20179962,36982484,11695996,17023049,21743453,14708096,12208234,25086907,32381029,17984046,15299003,9436456,12161072,15269663,26825125,17693412,26381711,16958617,25627681,27276257,33825858,24124794,20023768,15175001,14641996,16621918,12732639,12614169,18171728,11725864,35549722,25411383,21768539,12810058,18171678,29674523,10473562,9497245,19303294,32764093,31903994,31841587,11928716,12566385,21149547,19237502,22139840,20479108,11575529,20479110,24441828,22547813,22131268,23159934,31299492,12123492,33547325,31230402,12059893,15611117,15731587,31165076,30329129,21969454,12220451,10097181,10618932,9307036,11159936,26348911,11709545,31635807,21157159,18306019,34980804,12707260,19246389,36292611,23308296,22174035,24521037,21659649,28082361,7849712,15215235,30588601,19567749,29255089,12883402,23183335,10567689,34257294,15448513,17942409,20978128,21514828,24509862,11389482,32878990,22913516,17921453,17033962,16940308,34166122,24361844,28403410,23585572,12167662,20681998,34022226,17452324,20961976,15677376,25735680,11145921,9855701,9389851,25955245,28465322,19027160,9030597,15894801,27927985,12709367,34162222,14532276,35925888,27789712,8669678,10700782,24561095,30788618,35446340,9831351,19661110,33490280,24433488,23476141,12213830,19513315,29355282,9520251,16732090,21862589,29344738,23509717,7751854,8592342,18564801,12108947,7979121,11525881,11814342,9837897,17122579,21088110,31206373,10336416,30341173,24091937,11673462,37122213,21262961,9822655,11427530,33176865,18193641,8981316,34348614,28292875,24896116,9106529,15604937,14661655,32665491,14985404,34813985,17204937,24124188,19685112,1589759,9147872,24972488,36200983,33278783,33458582,22374134,28326467,33686871,25480325,12066726,25047158,10922003,14531168,10793526,18084979,34809703,29921212,32826313,16945924,11591164,9541102,29576327,10766778,22203976,34127251,22773841,34256322,10951187,12169641,19417098,32097819,12694155,24819467,30038012,36311249,35457253,11725865,16737973,20404344,32919876,35666680,29593014,21048710,20482855,17293538,10518010,18945287,27761157,25189431,33184643,23329375,1329295,23258540,28476886,34793835,31763755,23628358,19296124,22286060,21795085,29930394,23805838,12761215,8053891,34414986,23239586,26799446,31337666,26565425,20427316,25084811,15226293,12565913,21918424,18326664,36223685,23919265,24559985,19252784,29540372,25424378,25960145,7554356,33310301,32899693,7889656,31044239,16244001,36842386,17631035,27760856,32980662,23204524,19966218,25658027,12324472,23943880,33259453,32557910,35222090,12459180,1354642,12719381,7586638,33625594,1862346,7887423,35953818,19053230,23319589,22349750,19762757,30798905,36208971,32832689,30805902,30015672,30236257,23247425,31263958,35428369,23553484,26009541,28758053,35738978,31304636,36384028,31677658,30459030,19390614,25331388,33190635,32236737,25564733,9607712,18394989,12136074,18621707,29701772,16157601,11673493,23704352,32019969,23724080,11964232,36584481,18787086,1889818,10869186,19645060,26785433,14557272,15220814,36167878,30842289,23152933,35361824,16310654,33512901,30909845,19959667,19332786,32305961,36201369,11035031,34535181,32499372,27857962,23144945,25132084,21271335,34705503,34180878,22719904,33037202,12883401,21998699,28750945,15131021,10823104,24706162,32655342,31874912,35677449,19823671,1639409,32367593,23198031,36450915,10097041,28096415,28713282,20861418,29796677,14670767,20724266,10643591,32632746,33557936,28902675,36035384,35356048,35627144,21157006,30406384,25148524,34725342,32442084,2164719,30301919,8117533,9660811,36669590,30271978,26075051,10734096,29635721,21248738,25628744,15197184,10638927,23422674,7767091,33664309,1709891,30168660,7672403,29169929,24004537,28487634,33767344,30542613,30578099,20045464,29456480,1483040,29465616,24951453,32367466,35773764,21818084,24139989,32054689,36516687,14570802,8669666,31191425,22036948,32535660,18696266,34210543,35718563,11088018,30155738,11448278,36732880,35178478,35966320,21989361,18948004,31004442,37154182,35144690,20443062,18441289,36965156,12467748,34090936,34985200,32187740,29193480,35780681,17122568,31335544,15043482,35112786,34193198,21603587,30466856,26416891,35989752,36369638,14987556,30155320,28122814,9788730,31737266,32307305,32174957,17923728,34760638,29629541,28536299,25418085,34483938,33905995,32341817,30236493,27500320,10936352,36245440,29881197,33109742,34778666,33135148,26588645[uid]

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Reduced threshold for store overload-induced Ca²⁺ release is a common defect of RyR1 mutations associated with malignant hyperthermia and central core disease.

Chen W, Koop A, Liu Y, Guo W, Wei J, Wang R, MacLennan DH, Dirksen RT, Chen SRW. Chen W, et al. Biochem J. 2017 Aug 7;474(16):2749-2761. doi: 10.1042/BCJ20170282. Biochem J. 2017. PMID: 28687594 Free PMC article.

Reduced threshold for luminal Ca2+ activation of RyR1 underlies a causal mechanism of porcine malignant hyperthermia.

Jiang D, Chen W, Xiao J, Wang R, Kong H, Jones PP, Zhang L, Fruen B, Chen SR. Jiang D, et al. J Biol Chem. 2008 Jul 25;283(30):20813-20. doi: 10.1074/jbc.M801944200. Epub 2008 May 27. J Biol Chem. 2008. PMID: 18505726 Free PMC article.

Genotype-Phenotype Correlations of Malignant Hyperthermia and Central Core Disease Mutations in the Central Region of the RYR1 Channel.

Murayama T, Kurebayashi N, Ogawa H, Yamazawa T, Oyamada H, Suzuki J, Kanemaru K, Oguchi K, Iino M, Sakurai T. Murayama T, et al. Hum Mutat. 2016 Nov;37(11):1231-1241. doi: 10.1002/humu.23072. Epub 2016 Sep 19. Hum Mutat. 2016. PMID: 27586648

Distinct effects on Ca2+ handling caused by malignant hyperthermia and central core disease mutations in RyR1.

Dirksen RT, Avila G. Dirksen RT, et al. Biophys J. 2004 Nov;87(5):3193-204. doi: 10.1529/biophysj.104.048447. Epub 2004 Sep 3. Biophys J. 2004. PMID: 15347586 Free PMC article.

Nebivolol suppresses cardiac ryanodine receptor-mediated spontaneous Ca2+ release and catecholaminergic polymorphic ventricular tachycardia.

Tan Z, Xiao Z, Wei J, Zhang J, Zhou Q, Smith CD, Nani A, Wu G, Song LS, Back TG, Fill M, Chen SR. Tan Z, et al. Biochem J. 2016 Nov 15;473(22):4159-4172. doi: 10.1042/BCJ20160620. Epub 2016 Sep 13. Biochem J. 2016. PMID: 27623776 Free PMC article.

Skeletal and cardiac ryanodine receptors exhibit different responses to Ca2+ overload and luminal ca2+.

Kong H, Wang R, Chen W, Zhang L, Chen K, Shimoni Y, Duff HJ, Chen SR. Kong H, et al. Biophys J. 2007 Apr 15;92(8):2757-70. doi: 10.1529/biophysj.106.100545. Epub 2007 Jan 26. Biophys J. 2007. PMID: 17259277 Free PMC article.

RYR1 mutations causing central core disease are associated with more severe malignant hyperthermia in vitro contracture test phenotypes.

Robinson RL, Brooks C, Brown SL, Ellis FR, Halsall PJ, Quinnell RJ, Shaw MA, Hopkins PM. Robinson RL, et al. Hum Mutat. 2002 Aug;20(2):88-97. doi: 10.1002/humu.10098. Hum Mutat. 2002. PMID: 12124989

Functional effects of central core disease mutations in the cytoplasmic region of the skeletal muscle ryanodine receptor.

Avila G, Dirksen RT. Avila G, et al. J Gen Physiol. 2001 Sep;118(3):277-90. doi: 10.1085/jgp.118.3.277. J Gen Physiol. 2001. PMID: 11524458 Free PMC article.

Ryanodine receptor mutations in malignant hyperthermia and central core disease.

McCarthy TV, Quane KA, Lynch PJ. McCarthy TV, et al. Hum Mutat. 2000;15(5):410-7. doi: 10.1002/(SICI)1098-1004(200005)15:5<410::AID-HUMU2>3.0.CO;2-D. Hum Mutat. 2000. PMID: 10790202 Review.

The CPVT-associated RyR2 mutation G230C enhances store overload-induced Ca2+ release and destabilizes the N-terminal domains.

Liu Y, Kimlicka L, Hiess F, Tian X, Wang R, Zhang L, Jones PP, Van Petegem F, Chen SR. Liu Y, et al. Biochem J. 2013 Aug 15;454(1):123-31. doi: 10.1042/BJ20130594. Biochem J. 2013. PMID: 23746327

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