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And, mitochondria have a major function in executing the complex processes of neurotransmission and plasticity. We have previously demonstrated that Iptakalim (Ipt), a new ATP\u2010sensitive potassium (K\u2010ATP) channel opener, could improve the depressive\u2010like behavior in mice. But the underlying mechanisms are not well understood. The present study demonstrated that Ipt reversed depressive\u2010like phenotype in vivo (chronic mild stress\u2010induced mice model of depression) and in vitro (corticosterone\u2010induced cellular model). Further study showed that Ipt could upregulate the synaptic\u2010related proteins postsynaptic density 95 (PSD 95) and synaptophysin (SYN), and alleviated the synaptic structure damage. Moreover, Ipt could reverse the abnormal mitochondrial fission and fusion, as well as the reduced mitochondrial ATP production and collapse of mitochondrial membrane potential in depressive models. Knocking down the mitochondrial ATP\u2010sensitive potassium (Mito\u2010KATP) channel subunit MitoK partly blocked the above effects of Ipt. Therefore, our results reveal that Ipt can alleviate the abnormal mitochondrial dynamics and function depending on MitoK, contributing to improve synaptic plasticity and exert antidepressive effects. These findings provide a candidate compound and a novel target for antidepressive therapy.<\/jats:p>","DOI":"10.1096\/fj.202100124rr","type":"journal-article","created":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T10:22:05Z","timestamp":1618827725000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Iptakalim alleviates synaptic damages via targeting mitochondrial ATP\u2010sensitive potassium channel in depression"],"prefix":"10.1096","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5255-2865","authenticated-orcid":false,"given":"Wei","family":"Guo","sequence":"first","affiliation":[{"name":"Neuroprotective Drug Discovery Key Laboratory Jiangsu Key Laboratory of Neurodegeneration Center for Global Health Nanjing Medical University Nanjing 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