{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T15:41:52Z","timestamp":1747150912968,"version":"3.40.5"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,9,18]],"date-time":"2021-09-18T00:00:00Z","timestamp":1631923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>Both neuromuscular junction (NMJ) dysfunction and altered electrophysiological properties of muscle fibers have been reported in amyotrophic lateral sclerosis (ALS) patients. ALS\u2010related preclinical studies typically use rodent SOD1<jats:sup>G93A<\/jats:sup> overexpression models, but translation to the human disease has been challenged. The present work explored NMJ function and cellular electrophysiological properties of muscles fibers in SOD1<jats:sup>G93A<\/jats:sup> overexpression rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Longitudinal studies of compound muscle action potentials (CMAPs) were performed in SOD1<jats:sup>G93A<\/jats:sup> rats. Cellular studies were performed to evaluate electrophysiological properties of muscle fibers, including the resting membrane conductance (<jats:italic>G<\/jats:italic><jats:sub>m<\/jats:sub>) and its regulation during prolonged action potential (AP) firing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SOD1<jats:sup>G93A<\/jats:sup> rats showed a substantial loss of gastrocnemius CMAP amplitude (35.8\u2009mV, <jats:italic>P<\/jats:italic>\u00a0&lt;\u2009.001) and a minor increase in CMAP decrement (8.5%, <jats:italic>P<\/jats:italic>\u00a0=\u2009.002) at 25\u2009weeks. In addition, SOD1<jats:sup>G93A<\/jats:sup> EDL muscle fibers showed a lower baseline <jats:italic>G<\/jats:italic><jats:sub>m<\/jats:sub> (wild\u2010type, 1325\u2009\u03bcS\/cm<jats:sup>2<\/jats:sup>; SOD1<jats:sup>G93A<\/jats:sup>, 1137\u2009\u03bcS\/cm<jats:sup>2<\/jats:sup>; <jats:italic>P<\/jats:italic>\u00a0&lt;\u2009.001) and minor alterations in <jats:italic>G<\/jats:italic><jats:sub>m<\/jats:sub> regulation during repeated firing of APs as compared with wild\u2010type rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The current data suggest that loss of CMAP amplitude is largely explained by defects in either lower motor neuron or skeletal muscle with only minor indications of a role for neuromuscular transmission defects in SOD1<jats:sup>G93A<\/jats:sup> rats. Electrophysiological properties of muscle fibers were not markedly affected, and an elevated <jats:italic>G<\/jats:italic><jats:sub>m<\/jats:sub>, as has been reported in motor neuron disease (MND) patients, was not replicated in SOD1<jats:sup>G93A<\/jats:sup> muscles. Collectively, the neuromuscular pathology of SOD1<jats:sup>G93A<\/jats:sup> rats appears to differ from that of ALS\/MND patients with respect to neuromuscular transmission defects and electrophysiological properties of muscle fibers.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27413","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T05:45:24Z","timestamp":1630907124000},"page":"755-764","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Alterations in fast\u2010twitch muscle membrane conductance regulation do not explain decreased muscle function of <scp>SOD1<sup>G93A<\/sup><\/scp> rats"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0145-742X","authenticated-orcid":false,"given":"Pieter A.","family":"Leermakers","sequence":"first","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Skov","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Riisager","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ole B.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas H.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,9,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12350"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12551-013-0135-x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880020303"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880170708"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.9.10.627"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.57.5.897"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2011.05.019"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4103\/0366-6999.240798"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2017.07.007"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00252"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2008.01.001"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq106"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.09.002"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7054"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26365"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.69.3.325"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880070110"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1971.sp009667"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00501271"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1960.sp006424"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200910290"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP271556"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200910291"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.00541"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-39676-3"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.032539299"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201210918"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1982.sp014399"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00663.2010"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.280529"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-53235-w"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0860-18.2018"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20708"}],"container-title":["Muscle &amp; 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