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This can be observed in heat stress experiments, where the thermal inactivation of SERCA is linked to an increased production of reactive oxygen species. Previous studies have shown that regulatory proteins, including phospholamban (PLN) and heat shock protein 70 (Hsp70), can physically bind to SERCA2, preserving its function in the face of heat stress. Furthermore, we have demonstrated that the inhibition of glycogen synthase kinase 3\u03b2 (GSK3\u03b2) can alter the protein levels of PLN and HSP70 in cardiac tissues obtained from male mice; however, its potential downstream effects on the thermal inactivation of SERCA have not yet been investigated. In the present study, we examined the potential effects of GSK3\u03b2 inhibition through six weeks of low-dose lithium chloride supplementation (LiCl, 10\u00a0mg\/kg body mass\/day via drinking water) on the thermal inactivation of left ventricle SERCA2 obtained from male C57BL\/6J mice. Our results show that LiCl supplementation increased inhibitory serine 9 phosphorylation on GSK3\u03b2 while also significantly raising SERCA2 content and the SERCA2:PLN ratio. There were no changes to Hsp70 with LiCl supplementation. Although LiCl decreased baseline maximal SERCA activity, the decline in activity in response to heat stress was less compared with control. In conclusion, GSK3\u03b2 inhibition with LiCl is associated with protection of SERCA from thermal inactivation in the heart, and future studies should explore the underlying cellular mechanisms.<\/jats:p>","DOI":"10.1042\/bsr20253525","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:27:49Z","timestamp":1776853669000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of low-dose lithium supplementation on thermal inactivation of SERCA in cardiac muscle of male mice"],"prefix":"10.1042","volume":"46","author":[{"given":"Sophie\u00a0I.","family":"Hamstra","sequence":"first","affiliation":[{"name":"1Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, Canada"},{"name":"2Department of Kinesiology, Faculty of Applied Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mia\u00a0S.","family":"Geromella","sequence":"additional","affiliation":[{"name":"1Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, Canada"},{"name":"2Department of Kinesiology, Faculty of Applied Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panagiota","family":"Klentrou","sequence":"additional","affiliation":[{"name":"1Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, Canada"},{"name":"2Department of Kinesiology, Faculty of Applied Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter\u00a0M.","family":"Tiidus","sequence":"additional","affiliation":[{"name":"2Department of Kinesiology, Faculty of Applied Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca\u00a0E.K.","family":"MacPherson","sequence":"additional","affiliation":[{"name":"3Department of Health Sciences, Faculty of Applied Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4500-3347","authenticated-orcid":false,"given":"Val\u00a0A.","family":"Fajardo","sequence":"additional","affiliation":[{"name":"1Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, Canada"},{"name":"2Department of Kinesiology, Faculty of Applied Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"2026051303570250500_B1","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1139\/cjpp-2014-0463","article-title":"The regulation of sarco(endo)plasmic reticulum calcium-ATPases (SERCA)","volume":"93","author":"Stammers","year":"2015","journal-title":"Can. 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