TRP channels: sensors and transducers of gasotransmitter signals

Nobuaki Takahashi, Daisuke Kozai, Yasuo Mori

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 Ca(2+) 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 (O(2)) also control the activation of TRP channels. Anoxia induced by O(2)-glucose deprivation and severe hypoxia (1% O(2)) activates TRPM7 and TRPC6, respectively, whereas TRPA1 has recently been identified as a novel sensor of hyperoxia and mild hypoxia (15% O(2)) in vagal and sensory neurons. TRPA1 also detects other gaseous molecules such as hydrogen sulfide (H(2)S) and carbon dioxide (CO(2)). In this review, we focus on how signaling by gaseous molecules is sensed and integrated by TRP channels.