Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome/Myalgic encephalomyelitis patients

Biol Res. 2016 May 31;49(1):27. doi: 10.1186/s40659-016-0087-2.


Background: Transient receptor potential melastatin 3 (TRPM3) cation channels are ubiquitously expressed by multiple cells and have an important regulatory role in calcium-dependent cell signalling to help maintain cellular homeostasis. TRPM3 protein expression has yet to be determined on Natural Killer (NK) cells and B lymphocytes. Multiple single nucleotide polymorphisms have been reported in TRPM3 genes from isolated peripheral blood mononuclear cells, NK and B cells in Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) patients and have been proposed to correlate with illness presentation. The object of the study was to assess TRPM3 surface expression on NK and B lymphocytes from healthy controls, followed by a comparative investigation examining TRPM3 surface expression, and cytoplasmic and mitochondrial calcium influx in CD19(+) B cells, CD56(bright) and CD56(dim) cell populations from CFS/ME patients.

Results: TRPM3 cell surface expression was identified for NK and B lymphocytes in healthy controls (CD56(bright) TRPM3 35.72 % ± 7.37; CD56(dim) 5.74 % ± 2.00; B lymphocytes 2.05 % ± 0.19, respectively). There was a significant reduction of TRPM3 surface expression on CD19(+) B cells (1.56 ± 0.191) and CD56(bright) NK cells (17.37 % ± 5.34) in CFS/ME compared with healthy controls. Anti-CD21 and anti-IgM conjugated biotin was cross-linked with streptavidin,and subsequently treatment with thapsigargin. This showed a significant reduction in cytoplasmic calcium ion concentration in CD19(+) B lymphocytes. CD56(bright) NK cells also had a significant decrease in cytoplasmic calcium in the presence of 2-APB and thapsigargin in CFS/ME patients.

Conclusions: The results from this preliminary investigation identify, for the first time, TRPM3 surface expression on both NK and B lymphocytes in healthy controls. We also report for the first time, significant reduction in TRPM3 cell surface expression in NK and B lymphocytes, as well as decreased intracellular calcium within specific conditions in CFS/ME patients. This warrants further examination of these pathways to elucidate whether TRPM3 and impaired calcium mobilisation has a role in CFS/ME.

Keywords: Calcium signalling; Chronic fatigue syndrome; Myalgic encephalomyelitis; Transient receptor potential.

MeSH terms

  • Analysis of Variance
  • B-Lymphocytes / metabolism*
  • Calcium Channels / blood
  • Case-Control Studies
  • Enzyme Inhibitors / therapeutic use
  • Fatigue Syndrome, Chronic / blood*
  • Fatigue Syndrome, Chronic / drug therapy
  • Female
  • Flow Cytometry / methods
  • Humans
  • Immunophenotyping / methods
  • Killer Cells, Natural / metabolism*
  • Male
  • Middle Aged
  • Reference Values
  • TRPM Cation Channels / metabolism*
  • Thapsigargin / therapeutic use


  • Calcium Channels
  • Enzyme Inhibitors
  • TRPM Cation Channels
  • TRPM3 protein, human
  • Thapsigargin