Abstract
The transient receptor potential (trp) gene superfamily encodes cation channels that act as multimodal sensors for a wide variety of stimuli from outside and inside the cell. Upon sensing, they transduce electrical and Ca2+ signals via their cation channel activities. These functional features of TRP channels allow the body to react and adapt to different forms of environmental changes. Indeed, members of one class of TRP channels have emerged as sensors of gaseous messenger molecules that control various cellular processes. Nitric oxide (NO), a vasoactive gaseous molecule, regulates TRP channels directly via cysteine (Cys) S-nitrosylation or indirectly via cyclic GMP (cGMP)/protein kinase G (PKG)-dependent phosphorylation. Recent studies have revealed that changes in the availability of molecular oxygen (O2) also control the activation of TRP channels. Anoxia induced by O2-glucose deprivation and severe hypoxia (1% O2) activates TRPM7 and TRPC6, respectively, whereas TRPA1 has recently been identified as a novel sensor of hyperoxia and mild hypoxia (15% O2) in vagal and sensory neurons. TRPA1 also detects other gaseous molecules such as hydrogen sulfide (H2S) and carbon dioxide (CO2). In this review, we focus on how signaling by gaseous molecules is sensed and integrated by TRP channels.
Highlights
Transient receptor potential (TRP) proteins are the product of trp genes, which were first discovered in Drosophila melanogaster, but later found to have homologs in other species
We have found an interaction of TRPC5 with caveolin-1 and endothelial NOS (eNOS) in co-immunoprecipitation experiments as well as by colocalization of TRPC5 with caveolin-1 in heterologous systems and bovine aortic endothelial cells (Mori et al, unpublished data)
Macroscopic and single-channel current recordings using patch clamp techniques have demonstrated that SNAP (100 μM)-induced inhibition of receptor-activated TRPC6 currents is abolished by pharmacological blockade of cyclic GMP (cGMP)/protein kinase G (PKG) signaling with 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1one (ODQ), 2,3,9,10,11,12-hexahydro-10R-methoxy-2,9dimethyl-1-oxo-9S,12R-epoxy-1H-diindolo[1, 2,3-fg:3,2,1 -kl] pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester (KT5823) or membrane permeable PKG inhibitory peptide (DT3)
Summary
Transient receptor potential (TRP) proteins are the product of trp genes, which were first discovered in Drosophila melanogaster, but later found to have homologs in other species These gene products form cation channels that detect and transduce cellular stimuli into electrical signals (via changes in membrane potential) or chemical signals [via changes in intracellular Ca2+ concentration ([Ca2+]i)] (Montell et al, 2002; Clapham, 2003; Voets et al, 2005). TRP channels comprise six related protein subfamilies: TRPC, TRPV, TRPM, TRPA, TRPP, and TRPML (Clapham et al, 2005) (Figure 1B). The sole member of the TRPA subfamily, TRPA1, has a large N-terminal domain with 17 predicted ankyrin repeat (AnkR) domains (Gaudet, 2008) Pungent compounds, such as the allyl isothiocyanate found in mustard oil, trigger TRPA1 activation (Jordt et al, 2004). With the exception of TRPM4 and TRPM5 (Nilius, 2007), all of these TRP channels have some Ca2+ influx www.frontiersin.org
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