title: Activation, subunit composition and physiological relevance of DAG-sensitive TRPC proteins.
abstract: The classical transient receptor potential (TRP) protein family consists of seven members which share a common gating mechanism contingent on phospholipase C activation. While some family members are thought to be activated subsequent to emptying of intracellular calcium stores, others appear to be gated by as yet undefined lipid messengers. TRPC 3, 6 and 7 form a structural and functional TRPC subfamily characterized by their sensitivity towards diacylglycerols (DAGs). TRPC6 is a non-selective cation channel that is activated by DAG in a membrane-delimited fashion, independently of protein kinase C. Depletion of internal Ca2+ stores is not required for TRPC6 activity. TRPC6 mRNA and protein are abundantly expressed in smooth muscle cells and DAG-evoked Ca2+ transients can be observed in primary myocytes derived from lung and blood vessels. Thus, TRPC6 is a promising candidate for as yet unidentified non-selective cationic channels in smooth muscle cells potentially involved in vasoconstrictor-activated cation influx and myogenic tone of resistance arteries. Recent systematic studies revealed that TRPC proteins assemble into heteromultimers predominantly within the confines of distinct TRPC subfamilies. The known principles of channel complex formation will be instrumental in assessing the physiological role of distinct TRPC proteins in living cells.
authors.affiliation: Institut für Pharmakologie und Toxikologie, Fachbereich Medizin, Philipps-Universität Marburg, Karl-von-Frisch-Str. 1, 35033 Marburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gudermann
authors.forename: Thomas
authors.initials: T
authors.lastname: Hofmann
authors.forename: Michael
authors.initials: M
authors.lastname: Mederos y Schnitzler
authors.forename: Alexander
authors.initials: A
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling; D004075:Diglycerides / Q000494:pharmacology*; D005544:Forecasting; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; D050053:TRPM Cation Channels
chemical_list: C011439:1,2-diacylglycerol; D015220:Calcium Channels; D004075:Diglycerides; D007473:Ion Channels; D008565:Membrane Proteins; D021122:Protein Subunits; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; C498501:TRPC7 protein, human; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D002118:Calcium