Impaired calcium mobilization in natural killer cells from chronic fatigue syndrome/myalgic encephalomyelitis patients is associated with transient receptor potential melastatin 3 ion channels.

Transient receptor potential melastatin subfamily 3 (TRPM3) ion channels play a role in calcium (Ca ) cell signalling. Reduced TRPM3 protein expression has been identified in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) patients. However, the significance of TRPM3 and association with intracellular Ca mobilization has yet to be determined. Fifteen CFS/ME patients (mean age 48·82 ± 9·83 years) and 25 healthy controls (mean age 39·2 ± 12·12 years) were examined. Isolated natural killer (NK) cells were labelled with fluorescent antibodies to determine TRPM3, CD107a and CD69 receptors on CD56 CD16 NK cells and CD56 CD16 NK cells. Ca flux and NK cytotoxicity activity was measured under various stimulants, including pregnenolone sulphate (PregS), thapsigargin (TG), 2-aminoethoxydiphenyl borate (2APB) and ionomycin. Unstimulated CD56 CD16 NK cells showed significantly reduced TRPM3 receptors in CFS/ME compared with healthy controls (HC). Ca flux showed no significant difference between groups. Moreover, PregS-stimulated CD56 CD16 NK cells showed a significant increase in Ca flux in CFS/ME patients compared with HC. By comparison, unstimulated CD56 CD16 NK cells showed no significant difference in both Ca flux and TRPM3 expression. PregS-stimulated CD56 CD16 NK cells increased TRPM3 expression significantly in CFS/ME, but this was not associated with a significant increase in Ca flux. Furthermore, TG-stimulated CD56 CD16 NK cells increased K562 cell lysis prior to PregS stimulation in CFS/ME patients compared with HC. Differential expression of TRPM3 and Ca flux between NK cell subtypes may provide evidence for their role in the pathomechanism involving NK cell cytotoxicity activity in CFS/ME.