Role of TRP Channels in Respiratory Disease - Article Example

TRPV1 is activated by mediators like nerve growth factor, prostaglandin and bradykinin which lead to inflammation. In general, the family of TRPV contributes to respiratory diseases such as asthma, and COPD via induction of inflammatory response to agonists and cold. Introduction TRP Channels The family of transient receptor potential (TRP) ion channels comprises of approximately 28 mam­malian members and they can be subdivided into 6 subfamilies: 7 TRPC (canonical), 8 TRPM (melastatin), 6 TRPV (vanilloid), 1 TRPA (ankyrin), 2 TRPML (mucolipin) and 3 TRPP (polycystin).

Many invertebrate TRP channels have been identified in drosophila and ample evidence has emerged on the evolutionary conservation of the roles of TRP channels in sensory biology and cellular physiology. With respect to structure, TRP channels comprise carboxyl termini, intracellular amino and six transmembrane domains. Four subunits have a functional channel. Other unique features found in some TRP channels comprise a TRP domain located in the 6th transmembrane domain of some TRPM channels, and 3-14 ankyrin repeat domains in the amino terminus of TRPA, TRPV and TRPC channels.

Morphologically, TRP channels are can elicit different functions that can be mediated by hot/cold temperatures, voltage, osmolarity, ions, lipids, and G protein-coupled receptor (GPCR) signalling. When these TRP channels are activated, they mediate the influx of cations ( monovalent /divalent) into non-excitable and excitable cells (Sigma, n.d.). Figure 1 Schematic diagram of TRP channel. TRP subunits generally possess six transmembranes (TM) and there is a pore domain found between the segment fifth (S5) and sixth (S6) segments.

S1 has NH2 and S6 has COOH termini inside the cell. In 1977, the transient receptor potential (TRP) ion channels were first identified as a mutant of phototransduction in the photoreceptors or visual system of Drosophila (Moran et al. 2004; Gordon-Shaag et al. 2008). TRP channels are also commonly known as entry cation channels. In Drosophila, 13 TRP families are reported whereas in eukaryotes nearly 50 TRP channels are found from yeast to man. TRPs are also connected with other signalling mechanisms such as phospholipase C (PLC), G protein-coupled and growth factors (tyrosine kinase) receptors (Clapham et al.

2005; Nilius and Voets, 2005). TRP ion channels are expressed in different cell types and tissues (Caterina, 2006). They mediate various physiological processes such as ion homeostasis, and the sensation of stimuli. Most of these TRP channels are non-selective for cations with only a few being highly Ca2+ selective. Some TRP channels are permeable for hydrated Mg2+ ions. Modes of activation via gating mechanisms include temperature changes, covalent modification of nucleophilic residues, voltage or ligand binding.

Depolarization of the cellular membrane is mediated by activated TRP channels and this triggers the activation of voltage-dependent ion channels. This leads to a change in the intracellular Ca2+ concentration. The TRP channels serve as regulators for the transcellular transport of cations such as Mg2+ and Ca2+. In addition, they are essential for the optimal function of cellular organelles such as mitochondria, lysosomes, endosomes etc.