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Transient receptor potential melastatin 3 dysfunction in post COVID-19 condition and myalgic
Etianne Martini Sasso1,2,3, Katsuhiko Muraki4,5, Natalie Eaton-Fitch6,4
1The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia. e.martinisasso@griffith.edu.au.
Background:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe multisystemic condition associated with post-infectious onset, impaired natural killer (NK) cell cytotoxicity and impaired ion channel function, namely Transient Receptor Potential Melastatin 3 (TRPM3). Long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has resulted in neurocognitive, immunological, gastrointestinal, and cardiovascular manifestations recently recognised as post coronavirus disease 2019 (COVID-19) condition. The symptomatology of ME/CFS overlaps significantly with post COVID-19; therefore, this research aimed to investigate TRPM3 ion channel function in post COVID-19 condition patients.
Methods:
Whole-cell patch-clamp technique was used to measure TRPM3 ion channel activity in isolated NK cells of N = 5 ME/CFS patients, N = 5 post COVID-19 patients, and N = 5 healthy controls (HC). The TRPM3 agonist, pregnenolone sulfate (PregS) was used to activate TRPM3 function, while ononetin was used as a TRPM3 antagonist.
Results:
As reported in previous research, PregS-induced TRPM3 currents were significantly reduced in ME/CFS patients compared with HC (p = 0.0048). PregS-induced TRPM3 amplitude was significantly reduced in post COVID-19 condition compared with HC (p = 0.0039). Importantly, no significant difference was reported in ME/CFS patients compared with post COVID-19 condition as PregS-induced TRPM3 currents of post COVID-19 condition patients were similar of ME/CFS patients currents (p > 0.9999). Isolated NK cells from post COVID-19 condition and ME/CFS patients were resistant to ononetin and differed significantly with HC (p < 0.0001).
Conclusion:
The results of this investigation suggest that post COVID-19 condition patients may have impaired TRPM3 ion channel function and provide further evidence regarding the similarities between post COVID-19 condition and ME/CFS. Impaired TRPM3 channel activity in post COVID-19 condition patients suggest impaired ion mobilisation which may consequently impede cell function resulting in chronic post-infectious symptoms. Further investigation into TRPM3 function may elucidate the pathomechanism, provide a diagnostic and therapeutic target for post COVID-19 condition patients and commonalities with ME/CFS patients.
Insights
Patients with post coronavirus disease 2019 (COVID-19) condition exhibit impaired Transient Receptor Potential Melastatin 3 (TRPM3) ion channel function, similar to those with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This finding suggests a potential common pathway and therapeutic target for these debilitating post-infectious conditions.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe multisystemic illness characterized by impaired natural killer (NK) cell function and ion channel activity, specifically Transient Receptor Potential Melastatin 3 (TRPM3).
- Post coronavirus disease 2019 (COVID-19) condition, resulting from SARS-CoV-2 infection, presents with overlapping neurocognitive, immunological, and cardiovascular symptoms.
- Significant symptomatological overlap exists between ME/CFS and post COVID-19 condition, prompting investigation into shared underlying mechanisms.
Purpose of the Study:
- To investigate the function of the TRPM3 ion channel in patients diagnosed with post COVID-19 condition.
- To compare TRPM3 ion channel function in post COVID-19 patients with that of ME/CFS patients and healthy controls.
- To explore potential commonalities in the pathophysiology of post COVID-19 condition and ME/CFS.
Main Methods:
- Utilized the whole-cell patch-clamp technique to assess TRPM3 ion channel activity in isolated NK cells.
- Included participants diagnosed with ME/CFS, post COVID-19 condition, and healthy controls (n=5 per group).
- Employed pregnenolone sulfate (PregS) as a TRPM3 agonist and ononetin as a TRPM3 antagonist to modulate channel function.
Main Results:
- Pregnenolone sulfate-induced TRPM3 currents were significantly reduced in both ME/CFS and post COVID-19 patients compared to healthy controls.
- TRPM3 currents in post COVID-19 patients were comparable to those in ME/CFS patients, indicating no significant difference between the two groups.
- NK cells from both post COVID-19 and ME/CFS patients demonstrated resistance to the TRPM3 antagonist ononetin, differing significantly from healthy controls.
Conclusions:
- Impaired TRPM3 ion channel function is evident in patients with post COVID-19 condition, mirroring findings in ME/CFS.
- This suggests that altered ion channel activity may contribute to the chronic, post-infectious symptoms experienced by these patients.
- TRPM3 channel function represents a potential diagnostic biomarker and therapeutic target for post COVID-19 condition, highlighting commonalities with ME/CFS pathophysiology.
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