Channelpedia

PubMed 23417604


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPC , TRPC4



Title: An essential role of PI(4,5)P₂ for maintaining the activity of the transient receptor potential canonical (TRPC)4β.

Authors: Hana Kim, Jae-Pyo Jeon, Chansik Hong, Jinsung Kim, Jongyoun Myeong, Ju-Hong Jeon, Insuk So

Journal, date & volume: Pflugers Arch., 2013 Jul , 465, 1011-21

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23417604


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.