title: An essential role of PI(4,5)P₂ for maintaining the activity of the transient receptor potential canonical (TRPC)4β.
abstract: The transient receptor potential canonical 4 (TRPC4) channel is a Ca(2+)-permeable nonselective cation channel in mammalian cells and mediates a number of cellular functions. Many studies show that TRPC channels are activated by stimulation of Gαq-phospholipase C (PLC)-coupled receptors. However, our previous study showed that the TRPC4 current was inhibited by co-expression of a constitutively active form of Gαq (Gαq (Q209L)). A shortage of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] in Gαq (Q209L) may be responsible for reduced TRPC4 activity. Here, we tested this hypothesis by using a rapamycin-inducible system that regulates PI(4,5)P2 acutely and specifically. Our results showed that the TRPC4β current was reduced by inducible Gαq (Q209L), but not by the mutants with impaired binding ability to PLCβ. Depletion of PI(4,5)P2 by inducing the inositol polyphosphate 5-phosphatase to HEK293 cells that express TRPC4β led to an irreversible inhibition of TRPC4β currents. In contrast, inducing phosphatidylinositol 4-phosphate 5-kinase or intracellular PI(4,5)P2 application did not activate the TRPC4β current. Finally, we revealed that PI(4,5)P2 is important in delaying the desensitization of TRPC4β. Taken together, we suggest that PI(4,5)P2 is not the activator of TRPC4β activation, but it is still necessary for regulating TRPC4β activation.
authors: Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors: Hana
authors: H
authors: Kim
authors: Jae-Pyo
authors: JP
authors: Jeon
authors: Chansik
authors: C
authors: Hong
authors: Jinsung
authors: J
authors: Kim
authors: Jongyoun
authors: J
authors: Myeong
authors: Ju-Hong
authors: JH
authors: Jeon
authors: Insuk
authors: I
authors: So
mesh_terms: D000200:Action Potentials; D000818:Animals; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009154:Mutation; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D050052:TRPC Cation Channels / Q000378:metabolism*
chemical_list: D019269:Phosphatidylinositol 4,5-Diphosphate; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D043802:GTP-Binding Protein alpha Subunits, Gq-G11