Hydrogen sulfide, ME/CFS, POTS and TRPA1

Dysregulation of hydrogen sulfide, H(2)S, has been connected to ME/CFS in a hypothesis by Marian Lemle: Hypothesis: Chronic fatigue syndrome is caused by dysregulation of hydrogen sulfide metabolism.

And De Meirleir has created a hydrogen sulfide test for ME/CFS. Read more about it here Originator of H2S Theory Speaks and here ATP, Hydrogen Sulfide, Natural Killer Cells and the Heart.

Perhaps it is time to take a look at hydrogen sulfide and ME/CFS again, and POTS!

This study
Plasma hydrogen sulfide in differential diagnosis between vasovagal syncope and postural orthostatic tachycardia syndrome in children
showed, that plasma levels of H(2)S were significantly higher in children with vasovagal syncope (VVS) (95.3±3.8 μmol/L) and POTS (100.9±2.1 μmol/L) than in children in the control group (82.6±6.5 μmol/L). Compared with the VVS group, the POTS group had plasma levels of H(2)S that were significantly increased.

If we combine the hypothesis that elevated H(2)S is part of ME/CFS/POTS and the hypothesis that N-methyl-D-aspartate receptor is sensitized in ME, this article becomes very interesting:
Physiological role of hydrogen sulfide and polysulfide in the central nervous system:

• The researchers demonstrated that H(2)S is a neuromodulator that facilitates hippocampal long-term potentiation (LTP) by enhancing the activity of N-methyl-D-aspartate (NMDA) receptors.
• It also induces Ca2+ influx in the astrocytes by activating the transient receptor potential ankyrin-1 (TRPA1) channels.
• In addition, the article shows the recent findings that indicate that the H(2)S-derived polysulfides found in the brain activate TRPA1 channels more potently than parental H(2)S.

The observations from the study suggest that polysulfides derived from H(2)S activate TRPA1 channels to induce Ca2+ influx in astrocytes. Activated astrocytes, in turn, release D-serine to the synapse to enhance the activity of NMDA receptors.

Can we expand the old hypothesis: Dysregulated H(2)S is involved in excessive activation of TRPA1 and NMDA receptor in ME/CFS and POTS?

Endothelial and mithocondrial dysfunction is also suspected to be part of ME/CFS. H(2)S is a potent inhibitor of mitochondrial respiration, and H(2)S is involved in the NOS pathway.

Update 15. juni 2014: Problems with measurement of H2S: Controversies and Conundrums in Hydrogen Sulfide Biology

Further reading:

TRP blogposts - an overview

Hydrogen sulfide and translational medicine

Actions and interactions of nitric oxide, carbon monoxide and hydrogen sulphide in the cardiovascular system and in inflammation — a tale of three gases!

The anti-thrombotic effect of hydrogen sulfide is partly mediated by an upregulation of nitric oxide synthases

H2S Protects Against Pressure Overload Induced Heart Failure via Upregulation of Endothelial Nitric Oxide Synthase (eNOS)

High concentrations of hydrogen sulphide elevate the expression of a series of pro-inflammatory genes in fibroblast-like synoviocytes derived from rheumatoid and osteoarthritis patients

Hydrogen sulfide inhibits nitric oxide production and nuclear factor-kappaB via heme oxygenase-1 expression in RAW264.7 macrophages stimulated with lipopolysaccharide

TRP channels: sensors and transducers of gasotransmitter signals

H2S and its role in redox signaling