title: Activation of TRPC4β by Gαi subunit increases Ca2+ selectivity and controls neurite morphogenesis in cultured hippocampal neuron.
abstract: The ubiquitous transient receptor potential canonical (TRPC) channels function as non-selective, Ca(2+)-permeable channels. TRPC channels are activated by stimulation of Gαq-PLC-coupled receptors. Here, we report that TRPC4/TRPC5 can be activated by Gαi. We studied the essential role of Gαi subunits in TRPC4 activation and investigated changes in ion selectivity and pore dilation of the TRPC4 channel elicited by the Gαi2 subunit. Activation of TRPC4 by Gαi2 increased Ca2+ permeability and Ca2+ influx through TRPC4 channels. Co-expression of the muscarinic receptor (M2) and TRPC4 in HEK293 cells induced TRPC4-mediated Ca2+ influx. Moreover, both TRPC4β and the TRPC4β-Gαi2 signaling complex induced inhibition of neurite growth and arborization in cultured hippocampal neurons. Cells treated with KN-93, a CaMKII inhibitor, prevented TRPC4- and TRPC4-Gαi2(Q205L)-mediated inhibition of neurite branching and growth. These findings indicate an essential role of Gαi proteins in TRPC4 activation and extend our knowledge of the functional role of TRPC4 in hippocampal neurons.
authors.affiliation: Department of Physiology and Institute of Dermatological Science, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Jae-Pyo
authors.initials: JP
authors.lastname: Jeon
authors.forename: Seung-Eon
authors.initials: SE
authors.lastname: Roh
authors.forename: Jinhong
authors.initials: J
authors.lastname: Wie
authors.forename: Jinsung
authors.initials: J
authors.lastname: Kim
authors.forename: Hana
authors.initials: H
authors.lastname: Kim
authors.forename: Kyu-Pil
authors.initials: KP
authors.lastname: Lee
authors.forename: Dongki
authors.initials: D
authors.lastname: Yang
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
authors.forename: Nam-Hyuk
authors.initials: NH
authors.lastname: Cho
authors.forename: In-Gyu
authors.initials: IG
authors.lastname: Kim
authors.forename: David E
authors.initials: DE
authors.lastname: Kang
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Insuk
authors.initials: I
authors.lastname: So
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002414:Cations, Monovalent / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects*; D016062:Porosity; D011976:Receptors, Muscarinic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050052:TRPC Cation Channels / Q000378:metabolism*
chemical_list: D002414:Cations, Monovalent; D011976:Receptors, Muscarinic; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D019204:GTP-Binding Proteins; C498015:GNAI2 protein, human; D051960:GTP-Binding Protein alpha Subunit, Gi2; D002118:Calcium
keywords: Ca(2+)/calmodulin-dependent protein kinase; CaMK; Calcium; Dendrite; EGFP; G-protein-coupled receptor; GI; GPCR; GTPγS; Galphai2; Gi2; Neurite; PIP(2); PLC; PTX; TRPC; TRPC4; Transient receptor potential channel; enhanced GFP; gastrointestinal; guanosine5′-3-O-(thio)triphosphate; n.s.; not significant; pertussis toxin; phosphatidylinositol 4,5-bisphosphate; phospholipase C; transient receptor potential canonical