TRP channels Functions and involvement in neurologic disease

5-HT= : serotonin; ADPR= : adenosine diphosphate ribose; ATP= : adenosine triphosphate; cAMP= : cyclic adenosine monophosphate; CGRP= : calcitonin gene-related peptide; DAG= : diacylglycerol; DRG= : dorsal root ganglion; EP= : eicosanoid receptor; GPCR= : guanine nucleotide binding (G) protein-coupled receptors; IP3= : inositol triphosphate; NAD= : nicotinamide adenine dinucleotide; NADase= : NAD glycohydrolase; NGF= : nerve growth factor; nNOS= : nitric oxide synthase; NO= : nitric oxide; O2-= : superoxide ion; ONOO= : peroxinitrite; PARP-1= : polyADPR polymerase-1; PG= : prostaglandin; PIP2= : ; PK= : protein kinase; PLC= : phospholipase C; PTP= : permeability transition pore; ROS= : reactive oxygen species; trkA= : tyrosine kinase A; TRP= : transient receptor potential; TRPA= : TRP, ankyrin family; TRPC= : TRP, canonical family; TRPM= : TRP, melastatin family; TRPML= : TRP, mucolipin family; TRPP= : TRP, polycystin family; TRPV= : TRP, vanilloid family Transient receptor potential (TRP) channels are nonselective cation channels that function as cellular sensors that integrate diverse signals, including intracellular and extracellular messengers, exogenous chemicals, temperature, and mechanical stress. These channels are involved in multiple functions, including pain, temperature, and mechanical sensations, calcium (Ca2+) and magnesium (Mg2+) homeostasis, lysosomal function, cardiovascular regulation, and control of cell growth and proliferation.1–8 Not surprisingly, TRP channels have been implicated in a large variety of neurologic disorders, including neuropathic pain, cell injury during cerebral ischemia, and mucolipidosis type IV, a lysosomal storage disorder. The functions of the different families of TRP channels and their implications in disease have been comprehensively described in excellent recent reviews.1,2,5–8,10 The TRP channels are a superfamily of channels that allow influx of Ca2+ and sodium (Na+) both directly and indirectly by eliciting membrane depolarization. These channels consist of homo- or heterotetramers of subunits with six transmembrane domains that resemble those of voltage-gated cation channels.1–4 Mammalian TRP channels include several subfamilies, TRPC (classic or canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPP (polycystin), and TRPML (mucolipin).1–4 Each subfamily comprises several channel subtypes, which differ in their selectivity to Ca2+, conductance, activation mechanisms, and interacting proteins (table). These channels may be gated by several stimuli, including ligand binding to receptors that activate phospholipase C; direct activation by temperature and mechanical stimuli; products of lipid metabolism, such as anandamide or eicosanoids; and inorganic ions such as Ca2+ and Mg2+.3 Many TRP channels function as polymodal sensors that integrate many of these signals. The acid membrane phospholipid phosphatidylinositol 4,5 biphosphate (PIP2) has an important role in regulation of many TRP channels.1 Almost every TRP subunit is expressed in the nervous system. View this table: Table Representative examples of transient receptor …