Transient receptor potential channel

Transient receptor potential or TRP channels are a family of loosely related ion channels that are relatively non-selectively permeable to cations, including sodium, calcium and magnesium. TRP channels were initially discovered in trp mutant strain of a fruit fly, Drosophila. Later, TRP channels were found in vertebrates where they are ubiquitously expressed in many cell types and tissues. Most TRP channels are composed of 6 membrane-spanning helices with intracellular N- and C-termini. Mammalian TRP channels are activated and regulated by a wide variety of stimuli and are expressed throughout the body.

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TRP and TRP-like channels in insect vision

Figure 1. Light-activated TRPL channels in Periplaneta americana photoreceptors. A, a typical current through TRPL channels was evoked by a 4-s pulse of bright light (horizontal bar). B, a photoreceptor membrane voltage response to the light-induced activation of TRPL channels, data from the same cell are shown

The trp mutant fruit flies, that lack a functional copy of trp gene, are characterized by a transient response to light unlike wild-type flies that demonstrate a sustained photoreceptor activity in response to light.^[1] A distantly related isoform of TRP channel, TRP-like channel (TRPL) was later identified in Drosophila photoreceptors, where it is expressed at approximately 10 to 20-fold lower levels than TRP protein. A mutant fly, trpl, was subsequently isolated. Apart from structural differences, the TRP and TRPL channels differ in cation permeability and pharmacological properties.

TRP/TRPL channels are solely responsible for depolarization of insect photoreceptor plasma membrane in response to light. When these channels open, they let sodium and calcium to enter the cell down the concentration gradient, which depolarizes the membrane. Variations in light intensity become converted into the changes of number of open TRP/TRPL channels, and, therefore, into variations of membrane depolarization. These graded voltage responses propagate to photoreceptor synapses with second-order retinal neurons and further to the brain.
Importantly, mechanism of insect photoreception is dramatically different from that in mammals. Excitation of rhodopsin in mammalian photoreceptors leads to the hyperpolarization of the receptor membrane but not to depolarization like in the insect eye. In Drosophila and presumably other insects, a phospholipase C (PLC)-mediated signaling cascade links photoexcitation of rhodopsin to the opening of the TRP/TRPL channels. Although numerous activators of these channels such as phosphatidylinositol-4,5-bisphosphate (PIP₂) and polyunsaturated fatty acids (PUFAs) were known for years, a key factor mediating chemical coupling between PLC and TRP/TRPL channels remained a mystery until recently. It was found that a lipid product of PLC cascade, diacylglycerol (DAG), can directly activate TRP channels thus initiating membrane depolarization in response to light.^[2] This mechanism of TRP channel activation may be well preserved among other cell types where these channels perform various functions.

TRP genes in mammals

They are encoded by at least 33 channel subunit genes divided into seven sub-families:

• TRPC (canonical) - associated with Focal segmental glomerulosclerosis
• TRPV (vanilloid)
• TRPA (ankyrin)
• TRPM (melastatin) -- associated with Hypomagnesemia with secondary hypocalcemia
• TRPP (polycystin) -- associated with Polycystic kidney disease
• TRPML (mucolipin) -- associated with Mucolipidosis type IV
• TRPN (NOMPC) - no mechanoreceptor potential C - not found in mammals

References

External links

• MeSH Transient+Receptor+Potential+Channels
• "Transient Receptor Potential Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/IC/FamilyMenuForward?familyId=12.