title: Coassembly of Trp1 and Trp3 proteins generates diacylglycerol- and Ca2+-sensitive cation channels.
abstract: To analyze the functional consequences of coassembly of transient receptor potential 1 (Trp1) and Trp3 channel proteins, we characterized membrane conductances and divalent cation entry derived by separate overexpression and by coexpression of both Trp isoforms. Trp1 expression generated a 1-oleoyl-2-acetyl-sn-glycerol (OAG)-activated conductance that was detectable only in Ca(2+)-free extracellular solution. Trp3 expression gave rise to an OAG-activated conductance that was suppressed but clearly detectable at physiological Ca(2+) concentrations. Coexpression of both species resulted in a constitutively active, OAG-sensitive conductance, which exhibited distinctive cation selectivity and high sensitivity to inhibition by intracellular Ca(2+). Trp1-expressing cells displayed only modest carbachol-induced Ca(2+) entry and lacked OAG-induced Sr(2+) entry, whereas Trp3-expressing cells responded to both agents with a substantial divalent cation entry. Coexpression of Trp1 plus Trp3 suppressed carbachol-induced Ca(2+) entry compared with Trp3 expression and abolished OAG-induced Sr(2+) entry signals. We concluded that coassembly of Trp1 and Trp3 resulted in the formation of oligomeric Trp channels that are subject to regulation by phospholipase C and Ca(2+). The distinguished Ca(2+) sensitivity of these Trp1/Trp3 hetero-oligomers appeared to limit Trp-mediated Ca(2+) signals and may be of importance for negative feedback control of Trp function in mammalian cells.
authors.affiliation: Departments of Pharmacology und Toxikology and Medical Biochemistry and Medical Molecular Biology, University of Graz, Universitätsplatz 2, A-8010 Graz, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Lintschinger
authors.forename: M
authors.initials: M
authors.lastname: Balzer-Geldsetzer
authors.forename: T
authors.initials: T
authors.lastname: Baskaran
authors.forename: W F
authors.initials: WF
authors.lastname: Graier
authors.forename: C
authors.initials: C
authors.lastname: Romanin
authors.forename: M X
authors.initials: MX
authors.lastname: Zhu
authors.forename: K
authors.initials: K
authors.lastname: Groschner
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004075:Diglycerides / Q000494:pharmacology* / Q000502:physiology; D004330:Drosophila; D004533:Egtazic Acid / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013324:Strontium / Q000494:pharmacology; D050052:TRPC Cation Channels; D014162:Transfection
chemical_list: D015220:Calcium Channels; D004075:Diglycerides; D005656:Fungal Proteins; D011994:Recombinant Proteins; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C096351:transient receptor potential cation channel, subfamily C, member 1; D004533:Egtazic Acid; D002118:Calcium; D013324:Strontium