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Immunological disturbances such as persistent activation of immune cells and reduced cytotoxicity by natural killer (NK) cells are reported as key aspects in PCC. Recently, electrophysiological studies by our group demonstrated impairment of transient receptor potential melastatin 3 (TRPM3) ion channels in NK cells from PCC patients. The significant reduction in TRPM3 channel function and reduced functional activity by NK cells warrants further investigation. Hence, using live cell calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) imaging ex vivo, we examined the downstream impact of TRPM3 ion channel dysfunction on intracellular and mitochondrial Ca\n                    <jats:sup>2+<\/jats:sup>\n                    mobilization in NK cells from\n                    <jats:italic>N<\/jats:italic>\n                    = 8 PCC patients, age and sex matched to\n                    <jats:italic>N<\/jats:italic>\n                    = 8 PCC healthy controls (HC). Our findings provide new evidence of altered passive and TRPM3\u2010mediated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx, significantly impacting cytoplasmic and mitochondrial Ca\n                    <jats:sup>2+<\/jats:sup>\n                    mobilization in PCC. Passive cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx amplitude (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.0001) was significantly reduced in PCC; however, passive mitochondrial Ca\n                    <jats:sup>2+<\/jats:sup>\n                    mobilization (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.0001) was significantly increased. Importantly, cytoplasmic and mitochondrial response rates (slope,\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001) to pregnenolone sulphate stimulation were significantly reduced in PCC. Consequently, TRPM3\u2010dependent cytosolic (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001) and mitochondrial (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.0005) Ca\n                    <jats:sup>2+<\/jats:sup>\n                    mobilization were significantly reduced in PCC compared with HC. Altered ion channel Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signalling can severely impact both the immune system and bioenergetic processes, potentially leading to broader systemic dysregulations underpinning the pathomechanism of the PCC condition, and warrants further investigations.\n                  <\/jats:p>","DOI":"10.1002\/eji.70240","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:46:49Z","timestamp":1784728009000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered TRPM3\u2010Dependent Cytosolic and Mitochondrial Calcium Influx in Natural Killer Cells of Post\u2010COVID\u201019 Condition Patients"],"prefix":"10.1002","volume":"56","author":[{"given":"Chandi Tabeth","family":"Magawa","sequence":"first","affiliation":[{"name":"National Centre for Neuroimmunology and Emerging Diseases, Health Group Griffith University, Gold Coast Campus  Gold Coast Australia"},{"name":"Consortium Health International For Myalgic Encephalomyelitis Griffith University, Gold Coast Campus  Gold Coast Australia"},{"name":"School of Pharmacy and Medical Sciences Griffith University, Gold Coast Campus  Gold Coast Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Eaton\u2010Fitch","sequence":"additional","affiliation":[{"name":"National Centre for Neuroimmunology and Emerging Diseases, Health Group Griffith University, Gold Coast Campus  Gold Coast Australia"},{"name":"Consortium Health International For Myalgic Encephalomyelitis Griffith University, Gold Coast Campus  Gold Coast Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiko","family":"Muraki","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Pharmacology, School of Pharmacy Aichi\u2010Gakuin University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonya","family":"Marshall\u2010Gradisnik","sequence":"additional","affiliation":[{"name":"National Centre for Neuroimmunology and Emerging Diseases, Health Group Griffith University, Gold Coast Campus  Gold Coast Australia"},{"name":"Consortium Health International For Myalgic Encephalomyelitis Griffith University, Gold Coast Campus  Gold Coast Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00703-9"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/5578284"},{"key":"e_1_2_13_4_1","unstructured":"World Health Organization.A Clinical Case Definition of Post\u2010COVID\u201019 Condition by a Delphi Consensus 6 October 2021. 2021 [cited 2025 02 September];https:\/\/www.who.int\/publications\/i\/item\/WHO\u20102019\u2010nCoV\u2010Post_COVID\u201019_condition\u2010Clinical_case_definition\u20102021.1."},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01283-z"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2023.0750"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-043021-030635"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiac136"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(22)00127-8"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/PHM.0000000000001910"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-95565-8"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2022.101651"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.101019"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jim-2021-002051"},{"key":"e_1_2_13_15_1","unstructured":"National Institute for Health and Care Excellence N.COVID\u201019 Rapid Guideline: Managing the Long\u2010Term Effects of COVID\u201019. 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