{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:43:52Z","timestamp":1784259832752,"version":"3.55.0"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T00:00:00Z","timestamp":1714694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Recently, we reported that post COVID-19 condition patients also have Transient Receptor Potential Melastatin 3 (TRPM3) ion channel dysfunction, a potential biomarker reported in natural killer (NK) cells from Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS) patients. As there is no universal treatment for post COVID-19 condition, knowledge of ME\/CFS may provide advances to investigate therapeutic targets. Naltrexone hydrochloride (NTX) has been demonstrated to be beneficial as a pharmacological intervention for ME\/CFS patients and experimental investigations have shown NTX restored TRPM3 function in NK cells. This research aimed to: i) validate impaired TRPM3 ion channel function in post COVID-19 condition patients compared with ME\/CFS; and ii) investigate NTX effects on TRPM3 ion channel activity in post COVID-19 condition patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole-cell patch-clamp was performed to characterize TRPM3 ion channel activity in freshly isolated NK cells of post COVID-19 condition (<jats:italic>N<\/jats:italic> = 9; 40.56 \u00b1 11.26 years), ME\/CFS (<jats:italic>N<\/jats:italic> = 9; 39.33 \u00b1 9.80 years) and healthy controls (HC) (<jats:italic>N<\/jats:italic> = 9; 45.22 \u00b1 9.67 years). NTX effects were assessed on post COVID-19 condition (<jats:italic>N<\/jats:italic> = 9; 40.56 \u00b1 11.26 years) and HC (<jats:italic>N<\/jats:italic> = 7; 45.43 \u00b1 10.50 years) where NK cells were incubated for 24 hours in two protocols: treated with 200 \u00b5M NTX, or non-treated; TRPM3 channel function was assessed with patch-clamp protocol. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This investigation confirmed impaired TRPM3 ion channel function in NK cells from post COVID-19 condition and ME\/CFS patients. Importantly, PregS-induced TRPM3 currents were significantly restored in NTX-treated NK cells from post COVID-19 condition compared with HC. Furthermore, the sensitivity of NK cells to ononetin was not significantly different between post COVID-19 condition and HC after treatment with NTX.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings provide further evidence identifying similarities of TRPM3 ion channel dysfunction between ME\/CFS and post COVID-19 condition patients. This study also reports, for the first time, TRPM3 ion channel activity was restored in NK cells isolated from post COVID-19 condition patients after <jats:italic>in vitro<\/jats:italic> treatment with NTX. The TRPM3 restoration consequently may re-establish TRPM3-dependent calcium (Ca<jats:sup>2+<\/jats:sup>) influx. This investigation proposes NTX as a potential therapeutic intervention and TRPM3 as a treatment biomarker for post COVID-19 condition.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1264702","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T04:31:19Z","timestamp":1714710679000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Investigation into the restoration of TRPM3 ion channel activity in post-COVID-19 condition: a potential pharmacotherapeutic target"],"prefix":"10.3389","volume":"15","author":[{"given":"Etianne 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