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This study explored the protective effect of vagal nerve stimulation (<jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content>) against isoproterenol (<jats:styled-content style=\"fixed-case\">ISO<\/jats:styled-content>)\u2010induced myocardial ischaemia in a rat model and tested whether <jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content> plays a role in preventing disorders of mitochondrial dynamics and function. Isoproterenol not only caused cardiac injury but also increased the expression of mitochondrial fission proteins [dynamin\u2010related peptide1 (Drp1) and mitochondrial fission protein1 (Fis\u20101)) and decreased the expression of fusion proteins (optic atrophy\u20101 (<jats:styled-content style=\"fixed-case\">OPA<\/jats:styled-content>1) and mitofusins1\/2 (Mfn1\/2)], thereby disrupting mitochondrial dynamics and leading to increase in mitochondrial fragments. Interestingly, <jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content> restored mitochondrial dynamics through regulation of Drp1, Fis\u20101, <jats:styled-content style=\"fixed-case\">OPA<\/jats:styled-content>1 and Mfn1\/2; enhanced <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> content and mitochondrial membrane potential; reduced mitochondrial permeability transition pore (<jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content>) opening; and improved mitochondrial ultrastructure and size. Furthermore, <jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content> reduced the size of the myocardial infarction and ameliorated cardiomyocyte apoptosis and cardiac dysfunction induced by <jats:styled-content style=\"fixed-case\">ISO<\/jats:styled-content>. Moreover, <jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content> activated <jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>\u2010activated protein kinase (<jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content>), which was accompanied by phosphorylation of Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010dependent protein kinase kinase \u03b2 (Ca<jats:styled-content style=\"fixed-case\">MKK<\/jats:styled-content>\u03b2) during myocardial ischaemia. Treatment with subtype\u20103 of muscarinic acetylcholine receptor (M<jats:sub>3<\/jats:sub>R) antagonist 4\u2010diphenylacetoxy\u2010<jats:italic>N<\/jats:italic>\u2010methylpiperidine methiodide or <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> inhibitor Compound C abolished the protective effects of <jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content> on mitochondrial dynamics and function, suggesting that M<jats:sub>3<\/jats:sub>R\/Ca<jats:styled-content style=\"fixed-case\">MKK<\/jats:styled-content>\u03b2\/<jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> signalling are involved in mediating beneficial effects of <jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content>. This study demonstrates that <jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content> modulates mitochondrial dynamics and improves mitochondrial function, possibly through the M<jats:sub>3<\/jats:sub>R\/Ca<jats:styled-content style=\"fixed-case\">MKK<\/jats:styled-content>\u03b2\/<jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> pathway, to attenuate <jats:styled-content style=\"fixed-case\">ISO<\/jats:styled-content>\u2010induced cardiac damage in rats. Targeting mitochondrial dynamics may provide a novel therapeutic strategy in <jats:styled-content style=\"fixed-case\">IHD<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/jcmm.12938","type":"journal-article","created":{"date-parts":[[2016,8,5]],"date-time":"2016-08-05T06:07:35Z","timestamp":1470377255000},"page":"58-71","source":"Crossref","is-referenced-by-count":92,"title":["Vagal nerve stimulation improves mitochondrial dynamics <i>via<\/i> an M<sub>3<\/sub> receptor\/Ca<scp>MKK<\/scp>\u03b2\/<scp>AMPK<\/scp> pathway in isoproterenol\u2010induced myocardial ischaemia"],"prefix":"10.1111","volume":"21","author":[{"given":"Run\u2010Qing","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Xi'an Jiaotong University Health Science Center Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Xi'an Jiaotong University Health Science Center Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Jiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Xi'an Jiaotong University Health Science Center Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Ling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Xi'an Jiaotong University Health Science Center Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Jin","family":"Zang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Xi'an Jiaotong University Health Science Center Xi'an 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