torsdag den 4. april 2019

AMPK is a regulator of TRPA1

AMPK is a widely expressed intracellular energy sensor that monitors and modulates energy expenditure (1).

AMPK activation is impaired in muscle cell cultures derived from ME patients (2).

Transient receptor potential ankyrin 1 (TRPA1) channel is a widely recognized chemical and thermal sensor that plays vital roles in pain transduction (1).

Some ME patients have single nucleotide polymorphism in TRPA1 (3).

Wang et al discovered a functional link between AMPK and TRPA1 in dorsal root ganglion (DRG) neurons, in which AMPK activation rapidly resulted in downregulation of membrane-associated TRPA1 and its channel activity within minutes. Treatment with two AMPK activators, metformin or AICAR, inhibited TRPA1 activity in DRG neurons by decreasing the amount of membrane-associated TRPA1. Metformin induced a dose-dependent inhibition of TRPA1-mediated calcium influx (1).

Further reading:

2) Biosci Rep. 2018 May 8;38(3). pii: BSR20180242. doi: 10.1042/BSR20180242. Print 2018 Jun 29. Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS. Brown AE1, Dibnah B1, Fisher E1, Newton JL1,2, Walker M3,2.

3) Marshall-Gradisnk et al. Examination of Single Nucleotide Polymorphisms (SNPs) in Transient Receptor Potential (TRP) Ion Channels in Chronic Fatigue Syndrome Patients

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