Fig. 3

Presumed sodium load in ME/CFS at rest and during exercise in skeletal muscles. Intracellular sodium concentration in striated muscle in ME/CFS is presumably close to the threshold for reverse mode activation of the NCX or at least shows a very rapid rise at even low levels of exercise. This treshold is then rapidly crossed during exercise causing calcium overload which leads to mitochondrial and vascular dysfunction and muscular insulin resistance. The proximity of intracellular sodium concentration to this threshold is the presumed main cause for exercise intolerance in ME/CFS and the potential explanation for the characteristics of a threshold of effort for the induction of PEM