scholarly journals Transient Receptor Potential Ion Channels in the Etiology and Pathomechanism of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

2018 ◽  
Vol 09 (05) ◽  
pp. 445-453 ◽  
Author(s):  
D. Staines ◽  
S. Du Preez ◽  
H. Cabanas ◽  
C. Balinas ◽  
N. Eaton ◽  
...  
Keyword(s):  
Ion Channels ◽  
Chronic Fatigue Syndrome ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Fatigue Syndrome ◽  
Transient Receptor

scholarly journals Potential Implications of Mammalian Transient Receptor Potential Melastatin 7 in the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review

2021 ◽  
Vol 18 (20) ◽  
pp. 10708
Author(s):  
Stanley Du Preez ◽  
Helene Cabanas ◽  
Donald Staines ◽  
Sonya Marshall-Gradisnik
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Potential Candidate ◽  
Fatigue Syndrome ◽  
Organ Systems ◽  
Transient Receptor

The transient receptor potential (TRP) superfamily of ion channels is involved in the molecular mechanisms that mediate neuroimmune interactions and activities. Recent advancements in neuroimmunology have identified a role for TRP cation channels in several neuroimmune disorders including amyotropic lateral sclerosis, multiple sclerosis, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating disorder with an obscure aetiology, hence considerable examination of its pathobiology is warranted. Dysregulation of TRP melastatin (TRPM) subfamily members and calcium signalling processes are implicated in the neurological, immunological, cardiovascular, and metabolic impairments inherent in ME/CFS. In this review, we present TRPM7 as a potential candidate in the pathomechanism of ME/CFS, as TRPM7 is increasingly recognized as a key mediator of physiological and pathophysiological mechanisms affecting neurological, immunological, cardiovascular, and metabolic processes. A focused examination of the biochemistry of TRPM7, the role of this protein in the aforementioned systems, and the potential of TRPM7 as a molecular mechanism in the pathophysiology of ME/CFS will be discussed in this review. TRPM7 is a compelling candidate to examine in the pathobiology of ME/CFS as TRPM7 fulfils several key roles in multiple organ systems, and there is a paucity of literature reporting on its role in ME/CFS.

scholarly journals Potential Therapeutic Benefit of Low Dose Naltrexone in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Role of Transient Receptor Potential Melastatin 3 Ion Channels in Pathophysiology and Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Helene Cabanas ◽  
Katsuhiko Muraki ◽  
Natalie Eaton-Fitch ◽  
Donald Ross Staines ◽  
Sonya Marshall-Gradisnik
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Nk Cells ◽  
Low Dose ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Ionic Currents ◽  
Chronic Fatigue ◽  
Fatigue Syndrome ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating multi-systemic chronic condition of unknown aetiology classified as an immune dysfunction syndrome and neurological disorder. The discovery of the widely expressed Transient Receptor Potential Melastatin 3 (TRPM3) as a nociceptor channel substantially targeted by certain opioid receptors, and its implication in calcium (Ca2+)-dependent Natural Killer (NK) cell immune functions has raised the possibility that TRPM3 may be pharmacologically targeted to treat characteristic symptoms of ME/CFS. Naltrexone hydrochloride (NTX) acts as an antagonist to the mu (μ)-opioid receptor thus negating its inhibitory function on TRPM3. Based on the benefits reported by patients on their symptoms, low dose NTX (LDN, 3.0–5.0 mg/day) treatment seems to offer some potential benefit suggesting that its effect may be targeted towards the pathomechanism of ME/CFS. As there is no literature confirming the efficacy of LDN for ME/CFS patients in vitro, this study investigates the potential therapeutic effect of LDN in ME/CFS patients. TRPM3 ion channel activity was measured after modulation with Pregnenolone sulfate (PregS) and ononetin in NK cells on 9 ME/CFS patients taking LDN and 9 age- and sex-matched healthy controls using whole-cell patch-clamp technique. We report that ME/CFS patients taking LDN have restored TRPM3-like ionic currents in NK cells. Small ionic currents with a typical TRPM3-like outward rectification were measured after application of PregS, a TRPM3-agonist, in NK cells from patients taking LDN. Additionally, PregS-evoked ionic currents through TRPM3 were significantly modulated by ononetin, a TRPM3-antagonist, in NK cells from ME/CFS patients taking LDN. These data support the hypothesis that LDN may have potential as a treatment for ME/CFS by characterising the underlying regulatory mechanisms of LDN treatment involving TRPM3 and opioid receptors in NK cells. Finally, this study may serve for the repurpose of marketed drugs, as well as support the approval of prospective randomized clinical studies on the role and dose of NTX in treating ME/CFS patients.

scholarly journals Examination of Single Nucleotide Polymorphisms (SNPs) in Transient Receptor Potential (TRP) Ion Channels in Chronic Fatigue Syndrome Patients

2015 ◽  
Vol 7 ◽  
pp. III.S25147 ◽  
Author(s):  
Sonya M. Marshall-Gradisnik ◽  
Peter Smith ◽  
Ekua W. Brenu ◽  
Bernd Nilius ◽  
Sandra B. Ramos ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Single Nucleotide Polymorphisms ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Chronic Fatigue ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Fatigue Syndrome ◽  
Trp Ion Channels ◽  
Transient Receptor

Background The transient receptor potential (TRP) superfamily in humans comprises 27 cation channels with permeability to monovalent and divalent cations. These channels are widely expressed within humans on cells and tissues and have significant sensory and regulatory roles on most physiological functions. Chronic fatigue syndrome (CFS) is an unexplained disorder with multiple physiological impairments. OBJECTIVES The purpose of this study was to determine the role of TRPs in CFS. Methods The study comprised 115 CFS patients (age = 48.68 ± 1.06 years) and 90 nonfatigued controls (age = 46.48 ± 1.22 years). CFS patients were defined according to the 1994 Center for Disease Prevention and Control criteria for CFS. A total of 240 single nucleotide polymorphisms (SNPs) for 21 mammalian TRP ion channel genes ( TRPA1, TRPC1, TRPC2, TRPC3, TRPC4, TRPC6, TRPC7, TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPV1, TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6) were examined via the Agena Biosciences iPLEX Gold assay. Statistical analysis was performed using the PLINK analysis software. Results Thirteen SNPs were significantly associated with CFS patients compared with the controls. Nine of these SNPs were associated with TRPM3 (rs12682832; P < 0.003, rs11142508; P < 0.004, rs1160742; P < 0.08, rs4454352; P < 0.013, rs1328153; P < 0.013, rs3763619; P < 0.014, rs7865858; P ≤ 0.021, rs1504401; P ≤ 0041, rs10115622; P ≤ 0.050), while the remainder were associated with TRPA1 (rs2383844; P ≤ 0.040, rs4738202; P ≤ 0.018) and TRPC4 (rs6650469; P ≤ 0.016, rs655207; P ≤ 0.018). Conclusion The data from this pilot study suggest an association between TRP ion channels, predominantly TRPM3 and CFS. This and other TRPs identified may contribute to the etiology and pathomechanism of CFS.

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