新冠病毒感染后(post COVID-19)状况和肌痛性脑脊髓炎/慢性疲劳综合征(myalgic encephalomyelitis/chronic fatigue syndrome)患者中短暂感受器电位 melastatin 3 功能障碍。
Transient receptor potential melastatin 3 dysfunction in post COVID-19 condition and myalgic encephalomyelitis/chronic fatigue syndrome patients.
机构信息
The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia.
Consortium Health International for Myalgic Encephalomyelitis, National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia.
出版信息
Mol Med. 2022 Aug 19;28(1):98. doi: 10.1186/s10020-022-00528-y.
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.
背景
肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）是一种严重的多系统疾病，与感染后发病、自然杀伤（NK）细胞细胞毒性受损和离子通道功能受损有关，即瞬时受体电位 Melastatin 3（TRPM3）。严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）病毒的长期影响导致了最近被识别为新冠后疾病 2019（COVID-19）的神经认知、免疫、胃肠道和心血管表现。ME/CFS 的症状与新冠后重叠非常明显；因此，这项研究旨在调查新冠后患者中 TRPM3 离子通道功能。
方法
使用全细胞膜片钳技术测量 N = 5 例 ME/CFS 患者、N = 5 例新冠后患者和 N = 5 例健康对照（HC）的分离 NK 细胞中的 TRPM3 离子通道活性。使用孕烯醇酮硫酸盐（PregS）作为 TRPM3 激动剂来激活 TRPM3 功能，而 Ononetin 则用作 TRPM3 拮抗剂。
结果
正如之前的研究报道，与 HC 相比，PregS 诱导的 TRPM3 电流在 ME/CFS 患者中显着降低（p = 0.0048）。与 HC 相比，新冠后患者中 PregS 诱导的 TRPM3 幅度显着降低（p = 0.0039）。重要的是，与新冠后患者相比，ME/CFS 患者中没有报道显着差异，因为新冠后患者的 PregS 诱导的 TRPM3 电流与 ME/CFS 患者的电流相似（p>0.9999）。新冠后和 ME/CFS 患者的分离 NK 细胞对 Ononetin 有抗性，与 HC 有显着差异（p<0.0001）。
结论
这项研究的结果表明，新冠后患者可能存在 TRPM3 离子通道功能障碍，并提供了有关新冠后和 ME/CFS 之间相似性的进一步证据。新冠后患者中 TRPM3 通道活性受损表明离子迁移受损，这可能会阻碍细胞功能，导致慢性感染后症状。进一步研究 TRPM3 功能可能阐明发病机制，为新冠后患者提供诊断和治疗靶点，并阐明与 ME/CFS 患者的共同性。
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