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The present study tested the hypotheses that rapamycin\u2010mediated scar expansion was sex\u2010specific and that mTOR signaling directly influenced K<jats:sub>ATP<\/jats:sub> channel subunit expression\/activity. Scar size was significantly larger in post\u2010MI male rats as compared to the previous data reported in post\u2010MI female rats. The reported scar expansion of rapamycin\u2010treated post\u2010MI female rats was not observed following the administration of the macrolide to post\u2010MI male rats. Protein levels of the K<jats:sub>ATP<\/jats:sub> channel subunits Kir6.2 and SUR2A and phosphorylation of the serine<jats:sup>2448<\/jats:sup> residue of mTOR were similar in the normal heart of adult male and female rats. By contrast, greater tuberin inactivation characterized by the increased phosphorylation of the threonine<jats:sup>1462<\/jats:sup> residue and reduced raptor protein levels were identified in the normal heart of adult female rats. Rapamycin pretreatment of phorbol 12,13\u2010dibutyrate (PDBu)\u2010treated neonatal rat ventricular cardiomyocytes (NNVMs) suppressed hypertrophy, inhibited p70S6K phosphorylation, and attenuated SUR2A protein upregulation. In the presence of low ATP levels, K<jats:sub>ATP<\/jats:sub> channel activity detected in untreated NNVMs was significantly attenuated in PDBu\u2010induced hypertrophied NNVMs via a rapamycin\u2010independent pathway. Thus, rapamycin administration to post\u2010MI rats unmasked a sex\u2010specific pattern of scar expansion and mTOR signaling in PDBu\u2010induced hypertrophied NNVMs significantly increased SUR2A protein levels. However, the biological advantage associated with SUR2A protein upregulation was partially offset by an mTOR\u2010independent pathway that attenuated K<jats:sub>ATP<\/jats:sub> channel activity in PDBu\u2010induced hypertrophied NNVMs.<\/jats:p>","DOI":"10.1002\/iub.2722","type":"journal-article","created":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T14:35:45Z","timestamp":1680100545000},"page":"717-731","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rapamycin treatment unmasks a sex\u2010specific pattern of scar expansion of the infarcted rat heart: The relationship between <scp>mTOR<\/scp> and <scp>K<sub>ATP<\/sub><\/scp> channel"],"prefix":"10.1002","volume":"75","author":[{"given":"Aya","family":"Al\u2010Katat","sequence":"first","affiliation":[{"name":"Research Center Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"D\u00e9partement de 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