TRP channels: sensors and transducers of gasotransmitter signals

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.

Asymmetric dimethyl arginine induces pulmonary vascular dysfunction via activation of signal transducer and activator of transcription 3 and stabilization of hypoxia-inducible factor 1-alpha

“…The signaling pathway is associated with STAT3-dependent upregulation of TRPCencoded Ca 2+ channels which results in increase in cytosolically, nuclearly, and intracellularly stored Ca 2+ and may promote cell growth by moving quiescent cells into the cell cycle [36]. Besides that intracellular Ca 2+ serves as a shared signal transduction element that leads to elevated pulmonary vascular resistance in patients with PH [68][69][70][71]. Our study showed that ADMA and hypoxia were able to induce the upregulation of TRPC1, 3/6, associated with increased intracellular levels of Ca 2+ and enhanced proliferation of PASMC.…”

Redox regulation of transient receptor potential channels in the endothelium

“…The extracellular linker domain between the transmembrane domain S5 and S6 contains two cysteine residues (Cys 553 and Cys 558 ) that are potential targets for NO-dependent S-nitrosylation 43 . It has been suggested that when these residues are S-nitrosylated a disulfide bond forms in the linker region stabilizing the channel in the open configuration 86 . This NO-dependent mechanism could potentially have important physiological consequences in the endothelium.…”

Experimental Observations on the Biological Significance of Hydrogen Sulfide in Carotid Body Chemoreception

“…In addition, the recent description that sulfi de inhibits L-type voltage dependent Ca 2+ channels in several tissues (Zhang et al 2012 ;Streeter et al 2012 ;Tang et al 2013 ;Avanzato et al 2014 ) Kimura 2014 ). Additionally, TRPA1 can also be activated by hypoxia (Takahashi et al 2012 General procedures used to label chemoreceptor cells CA deposits and to later study their release have been described in previous publications (Vicario et al 2000 ) and analytical methods have been described in detail in Conde et al ( 2006 ). In brief, the CBs were incubated (2 h; 37 °C) in Tyrode solution containing 3 H-tyrosine (40-50 Ci/ mmol; Perkin-Elmer España), 6-methyltetrahydropterine (100 μM) and ascorbic acid (1 mM).…”