søndag den 9. september 2012

TRP Ion Channels

The cell communicates with the surroundings via receptors in the cell surface. Based on structural and functional similarities, membrane receptors are mainly divided into 3 classes: The ion channel-linked receptor, the enzyme-linked receptor and G protein-coupled receptor. Reference wikipedia.

TRP channels (transient receptor potential channels) - the family is subdivided into 6 subfamilies based on homology:
  • TRPC1-7, Canonical
  • TRPV1-6, Vanilloid
  • TRPM1-8, Melastatin
  • TRPP1-3, Polycystin
  • TRPML1-3, Mucolipin
  • TRPA1, Ankyrin
This TRP superfamily of ion channels play a crucial role in a broad range of sensory functions including vision, taste, olfaction, hearing, touch, pain and thermosensation. Reference.
Alan R. Light, Charles J. Vierck, and Kathleen C. Light have written about TRPV1s possible role in ME/CFS and comorbidities in Translation from Mouse Sensory Neurons to Fibromyalgia and Chronic Fatigue Syndromes.

I find TRP ion channels interesting because they are found in dorsal root ganglia and they are suspected to be involved with microglia activation as I wrote about in my last blogs. Pathophysiological roles of transient receptor potential channels in glial cells.

And TRP ion channel interact with G protein coupled receptors, which Professor Don Staines has hypothesised is involved in ME. Two to tango: GPCR oligomers and GPCR-TRP channel interactions in nociception.

Recent research shows that TRPV1 is a stress response protein in the central nervous system. TRPV1 is emerging as a key mediator of CNS function through modulation of both glial and neuronal activity. Growing evidence has suggested that TRPV1 can mediate a variety of pathways from glial reactivity and cytokine release to synaptic transmission and plasticity. Increasing evidence shows that TRPV1 is as a regulator of CNS function in response to stress. This article also suggests that TRPV1 is implicated in dopamine and glutamte release, and within the dorsal root ganglion, TRPV1 expression is localized to the C-and Aδ- fibers. Here, channel activation leads to calcium elevations and subsequent release of neuropeptides including calcitonin-gene-related peptide and substance P.

There is a book about TRP Channels here: TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades.

TRPA1 Mediates Mechanical Sensitization in Nociceptors during Inflammation:
"Inflammation is a part of the body's natural response to tissue injury which initiates the healing process. Unfortunately, inflammation is frequently painful and leads to hypersensitivity to mechanical stimuli, which is difficult to treat clinically. While it is well established that altered sensory processing in the spinal cord contributes to mechanical hypersensitivity (central sensitization), it is still debated whether primary afferent neurons become sensitized to mechanical stimuli after tissue inflammation....Our findings indicate that C-Mechano Cold sensitive fibers exhibit enhanced firing to suprathreshold mechanical stimuli in a TRPA1-dependent manner during inflammation, and that input from these fibers drives mechanical hyperalgesia in inflamed mice."

Ingen kommentarer:

Send en kommentar

Bemærk! Kun medlemmer af denne blog kan sende kommentarer.