title: Voltage-sensing phosphatase reveals temporal regulation of TRPC3/C6/C7 channels by membrane phosphoinositides.
abstract: TRPC3/C6/C7 channels, a subgroup of classical/canonical TRP channels, are activated by diacylglycerol produced via activation of phospholipase C (PLC)-coupled receptors. Recognition of the physiological importance of these channels has been steadily growing, but the mechanism by which they are regulated remains largely unknown. We recently used a membrane-resident danio rerio voltage-sensing phosphatase (DrVSP) to study TRPC3/C6/C7 regulation and found that the channel activity was controlled by PtdIns(4,5)P(2)-DAG signaling in a self-limiting manner (Imai Y et al., the Journal of Physiology, 2012). In this addendum, we present the advantages of using DrVSP as a molecular tool to study PtdIns(4,5)P(2) regulation. DrVSP should be readily applicable for studying phosphoinositide metabolism-linked channel regulation as well as lipid dynamics. Furthermore, in comparison to other modes of self-limiting ion channel regulation, the regulation of TRPC3/C6/C7 channels seems highly susceptible to activation signal strength, which could potentially affect both open duration and the time to peak activation and inactivation. Dysfunction of such self-limiting regulation may contribute to the pathology of the cardiovascular system, gastrointestinal tract and brain, as these channels are broadly distributed and affected by numerous neurohormonal agonists.
authors: Department of Physiology, School of Medicine, Fukuoka University, Japan.
authors: Kyohei
authors: K
authors: Itsuki
authors: Yuko
authors: Y
authors: Imai
authors: Yasushi
authors: Y
authors: Okamura
authors: Kihachiro
authors: K
authors: Abe
authors: Ryuji
authors: R
authors: Inoue
authors: Masayuki X
authors: MX
authors: Mori
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D002938:Ciona intestinalis; D004075:Diglycerides / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating; D051379:Mice; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D054801:Phosphoinositide Phospholipase C / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D013045:Species Specificity; D050052:TRPC Cation Channels / Q000378:metabolism*; D000074287:TRPC6 Cation Channel; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D004075:Diglycerides; D019269:Phosphatidylinositol 4,5-Diphosphate; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; C498502:Trpc7 protein, mouse; D029961:Zebrafish Proteins; C576619:tpte protein, zebrafish; C509671:voltage-sensor-containing phosphatase, Ciona intestinalis; D010744:Phosphoric Monoester Hydrolases; D054801:Phosphoinositide Phospholipase C