TRP channels in disease.
The mammalian TRP (transient receptor potential) family consists of six main subfamilies termed the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), and TRPA (ankyrin) groups. These subfamilies encompass 28 ion channels that function as diverse cellular sensors. All of the channels are permeable to monovalent cations, and most are also permeable to Ca(2+). There are strong indications that TRP channels are involved in many diseases. At this point, four channelopathies have been identified in which a defect in a TRP channel-encoding gene is the direct cause of disease. TRPs are also involved in some systemic diseases because of their role as receptors for irritants, inflammation products, and xenobiotic toxins. Other indications of the involvement of TRPs in several diseases come from correlations between the levels of channel expression and disease symptoms or from the mapping of TRP-encoding genes to susceptible chromosome regions. Finally, the phenotypes of TRP knockout mice and other transgenic models allow a degree of extrapolation to human diseases. We present an overview of current knowledge about the role of TRP channels in human disease and highlight some TRP "suspects" for which a role in disease can be anticipated. An understanding of the genetics of disease may lead to the development of targeted new therapies.
Nilius
Bernd
B
Department of Physiology, Campus Gasthuisberg Katholieke Universiteit, Leuven, Belgium. bernd.nilius@med.kuleuven.ac.be
Voets
Thomas
T
Peters
John
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D002318:Cardiovascular Diseases / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000378:metabolism; D034381:Hearing Loss / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D007674:Kidney Diseases / Q000378:metabolism; D008171:Lung Diseases / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D009619:Nociceptors / Q000502:physiology; D010146:Pain / Q000378:metabolism; D012678:Sensation Disorders / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D050053:TRPM Cation Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D050396:TRPP Cation Channels; D050916:TRPV Cation Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D050051:Transient Receptor Potential Channels / Q000145:classification / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001745:Urinary Bladder Diseases / Q000378:metabolism
D015220:Calcium Channels; D002412:Cations; C416674:MCOLN1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050052:TRPC Cation Channels; D050053:TRPM Cation Channels; D050396:TRPP Cation Channels; D050916:TRPV Cation Channels; D050051:Transient Receptor Potential Channels; D002118:Calcium