{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T18:06:37Z","timestamp":1769277997785,"version":"3.49.0"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2016,2,5]],"date-time":"2016-02-05T00:00:00Z","timestamp":1454630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0148161","type":"journal-article","created":{"date-parts":[[2016,2,5]],"date-time":"2016-02-05T19:10:30Z","timestamp":1454699430000},"page":"e0148161","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Blockage of the Ryanodine Receptor via Azumolene Does Not Prevent Mechanical Ventilation-Induced Diaphragm Atrophy"],"prefix":"10.1371","volume":"11","author":[{"given":"Erin E.","family":"Talbert","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley J.","family":"Smuder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oh Sung","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurt J.","family":"Sollanek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P.","family":"Wiggs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott K.","family":"Powers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2016,2,5]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1056\/NEJMoa070447","article-title":"Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans","volume":"358","author":"S Levine","year":"2008","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1164\/rccm.201002-0234OC","article-title":"Mechanical ventilation-induced diaphragm disuse in humans triggers autophagy","volume":"182","author":"SN Hussain","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"ref3","article-title":"Mitochondrial Dysfunction and Lipid Accumulation in the Human Diaphragm during Mechanical Ventilation","author":"M Picard","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1056\/NEJM199502093320601","article-title":"A comparison of four methods of weaning patients from mechanical ventilation. Spanish Lung Failure Collaborative Group","volume":"332","author":"A Esteban","year":"1995","journal-title":"N Engl J Med"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1097\/01.CCM.0000065188.87029.C3","article-title":"Morbidity, mortality, and quality-of-life outcomes of patients requiring >or = 14 days of mechanical ventilation","volume":"31","author":"A Combes","year":"2003","journal-title":"Crit Care Med"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.jtcvs.2009.05.034","article-title":"Prolonged mechanical ventilation after cardiac surgery: outcome and predictors","volume":"138","author":"JL Trouillet","year":"2009","journal-title":"J Thorac Cardiovasc Surg"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1164\/rccm.200407-939OC","article-title":"Trolox attenuates mechanical ventilation-induced diaphragmatic dysfunction and proteolysis","volume":"170","author":"JL Betters","year":"2004","journal-title":"Am J Respir Crit Care Med"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1164\/rccm.200202-088OC","article-title":"Mechanical ventilation-induced diaphragmatic atrophy is associated with oxidative injury and increased proteolytic activity","volume":"166","author":"RA Shanely","year":"2002","journal-title":"Am J Respir Crit Care Med"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1152\/japplphysiol.00098.2010","article-title":"Oxidative stress is required for mechanical ventilation-induced protease activation in the diaphragm","volume":"108","author":"MA Whidden","year":"2010","journal-title":"J Appl Physiol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1097\/CCM.0b013e3182190b62","article-title":"Mitochondria-targeted antioxidants protect against mechanical ventilation-induced diaphragm weakness","volume":"39","author":"SK Powers","year":"2011","journal-title":"Crit Care Med"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.freeradbiomed.2009.01.002","article-title":"Mechanical ventilation induces diaphragmatic mitochondrial dysfunction and increased oxidant production","volume":"46","author":"AN Kavazis","year":"2009","journal-title":"Free Radic Biol Med"},{"key":"ref12","article-title":"Cross-talk between the calpain and caspase-3 proteolytic systems in the diaphragm during prolonged mechanical ventilation","author":"WB Nelson","year":"2012","journal-title":"Crit Care Med"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1097\/00003677-200207000-00004","article-title":"Molecular events in skeletal muscle during disuse atrophy","volume":"30","author":"SC Kandarian","year":"2002","journal-title":"Exerc Sport Sci Rev"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1152\/jappl.1999.87.1.386","article-title":"Intracellular Ca2+ transients in mouse soleus muscle after hindlimb unloading and reloading","volume":"87","author":"CP Ingalls","year":"1999","journal-title":"J Appl Physiol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"493618","DOI":"10.1155\/2012\/493618","article-title":"Various jobs of proteolytic enzymes in skeletal muscle during unloading: facts and speculations","volume":"2012","author":"EV Kachaeva","year":"2012","journal-title":"J Biomed Biotechnol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1152\/physrev.00013.2002","article-title":"Ryanodine receptor calcium release channels","volume":"82","author":"M Fill","year":"2002","journal-title":"Physiol Rev"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.cmet.2011.05.014","article-title":"Ryanodine receptor oxidation causes intracellular calcium leak and muscle weakness in aging","volume":"14","author":"DC Andersson","year":"2011","journal-title":"Cell Metab"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/2044-5040-2-9","article-title":"Leaky ryanodine receptors in beta-sarcoglycan deficient mice: a potential common defect in muscular dystrophy","volume":"2","author":"DC Andersson","year":"2012","journal-title":"Skelet Muscle"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nm.1916","article-title":"Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle","volume":"15","author":"AM Bellinger","year":"2009","journal-title":"Nat Med"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"9607","DOI":"10.1073\/pnas.0500353102","article-title":"Enhancing calstabin binding to ryanodine receptors improves cardiac and skeletal muscle function in heart failure","volume":"102","author":"XH Wehrens","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1097\/00024382-200115030-00007","article-title":"Dantrolene reduces serum TNFalpha and corticosterone levels and muscle calcium, calpain gene expression, and protein breakdown in septic rats","volume":"15","author":"DR Fischer","year":"2001","journal-title":"Shock"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.beem.2012.05.003","article-title":"Cellular and molecular mechanisms of mitochondrial function","volume":"26","author":"LD Osellame","year":"2012","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"ref23","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-69945-5","article-title":"Mitochondria: The Dynamic Organelle","author":"S Schaffer","year":"2007"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"30715","DOI":"10.1074\/jbc.M709555200","article-title":"Impaired regulation of brain mitochondria by extramitochondrial Ca2+ in transgenic Huntington disease rats","volume":"283","author":"FN Gellerich","year":"2008","journal-title":"J Biol Chem"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1042\/bst0311300","article-title":"Mitochondrial matrix reactive oxygen species production is very sensitive to mild uncoupling","volume":"31","author":"S Miwa","year":"2003","journal-title":"Biochem Soc Trans"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1023\/A:1015921513720","article-title":"Control of mitochondrial membrane potential and ROS formation by reversible phosphorylation of cytochrome c oxidase","volume":"234\u2013235","author":"I Lee","year":"2002","journal-title":"Mol Cell Biochem"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.2741\/3303","article-title":"Crosstalk signaling between mitochondrial Ca2+ and ROS","volume":"14","author":"RF Feissner","year":"2009","journal-title":"Front Biosci (Landmark Ed)"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"26965","DOI":"10.1074\/jbc.272.43.26965","article-title":"Dantrolene inhibition of sarcoplasmic reticulum Ca2+ release by direct and specific action at skeletal muscle ryanodine receptors","volume":"272","author":"BR Fruen","year":"1997","journal-title":"J Biol Chem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1124\/jpet.105.084046","article-title":"Effects of azumolene on Ca2+ sparks in skeletal muscle fibers","volume":"314","author":"Y Zhang","year":"2005","journal-title":"J Pharmacol Exp Ther"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1111\/j.1476-5381.1989.tb12573.x","article-title":"The effect of EU4093 (azumolene sodium) on the contraction of intrafusal muscle in the soleus muscle of the anaesthetized rat","volume":"97","author":"GC Leslie","year":"1989","journal-title":"Br J Pharmacol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1152\/japplphysiol.00881.2001","article-title":"Mechanical ventilation results in progressive contractile dysfunction in the diaphragm","volume":"92","author":"SK Powers","year":"2002","journal-title":"J Appl Physiol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"C474","DOI":"10.1152\/ajpcell.1986.250.3.C474","article-title":"Architecture, composition, and contractile properties of rat soleus muscle grafts","volume":"250","author":"SS Segal","year":"1986","journal-title":"Am J Physiol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"C844","DOI":"10.1152\/ajpcell.00402.2005","article-title":"Type II skeletal myofibers possess unique properties that potentiate mitochondrial H(2)O(2) generation","volume":"290","author":"EJ Anderson","year":"2006","journal-title":"Am J Physiol Cell Physiol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1164\/rccm.200601-142OC","article-title":"Caspase-3 regulation of diaphragm myonuclear domain during mechanical ventilation-induced atrophy","volume":"175","author":"JM McClung","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"MM Bradford","year":"1976","journal-title":"Anal Biochem"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1113\/jphysiol.2014.286518","article-title":"Increased mitochondrial emission of reactive oxygen species and calpain activation are required for doxorubicin-induced cardiac and skeletal muscle myopathy","volume":"593","author":"K Min","year":"2015","journal-title":"J Physiol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1097\/CCM.0b013e3182374a84","article-title":"Nuclear factor-\u03baB signaling contributes to mechanical ventilation-induced diaphragm weakness*","volume":"40","author":"AJ Smuder","year":"2012","journal-title":"Crit Care Med"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1152\/japplphysiol.01086.2011","article-title":"Endurance exercise attenuates ventilator-induced diaphragm dysfunction","volume":"112","author":"AJ Smuder","year":"2012","journal-title":"J Appl Physiol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1152\/physrev.00029.2002","article-title":"The calpain system","volume":"83","author":"DE Goll","year":"2003","journal-title":"Physiol Rev"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"R464","DOI":"10.1152\/ajpregu.00231.2013","article-title":"Ventilator-induced diaphragm dysfunction: cause and effect","volume":"305","author":"SK Powers","year":"2013","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/j.1742-7843.2007.00156.x","article-title":"Effects of azumolene on normal and malignant hyperthermia-susceptible skeletal muscle","volume":"102","author":"RT Sudo","year":"2008","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1164\/ajrccm.149.6.8004310","article-title":"Effects of mechanical ventilation on diaphragmatic contractile properties in rats","volume":"149","author":"G Le Bourdelles","year":"1994","journal-title":"Am J Respir Crit Care Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0148161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T01:22:16Z","timestamp":1588987336000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0148161"}},"subtitle":[],"editor":[{"given":"Carlos E.","family":"Ambr\u00f3sio","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2016,2,5]]},"references-count":42,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2016,2,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0148161","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,5]]}}}