Activation of TRPC4β by Gαi subunit increases Ca2+ selectivity and controls neurite morphogenesis in cultured hippocampal neuron

• Published in: Cell calcium (Edinburgh) Vol. 54; no. 4; pp. 307 - 319
• Main Authors: Jeon, Jae-Pyo, Roh, Seung-Eon, Wie, Jinhong, Kim, Jinsung, Kim, Hana, Lee, Kyu-Pil, Yang, Dongki, Jeon, Ju-Hong, Cho, Nam-Hyuk, Kim, In-Gyu, Kang, David E, Kim, Hyun Jin, So, Insuk
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier India Pvt Ltd 01.10.2013
• Subjects: Advanced Basic Science; Animals; Calcium; Calcium - pharmacology; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; Cations, Monovalent - pharmacology; Cell Membrane Permeability - drug effects; Cells, Cultured; Dendrite; Dendrites - drug effects; Dendrites - metabolism; Galphai2; Gi2; GTP-Binding Protein alpha Subunit, Gi2 - metabolism; GTP-Binding Proteins - metabolism; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology; HEK293 Cells; Hippocampus - cytology; Humans; Ion Channel Gating - drug effects; Mice; Mice, Inbred C57BL; Neurite; Neurites - drug effects; Neurites - metabolism; Neurogenesis - drug effects; Porosity; Receptors, Muscarinic - metabolism; Signal Transduction - drug effects; Transient receptor potential channel; TRPC; TRPC Cation Channels - metabolism; TRPC4; PIP 2; CaMK; Neurite; Calcium; transient receptor potential canonical; PLC; G-protein-coupled receptor; EGFP; GTPγS; Transient receptor potential channel; PTX; TRPC; pertussis toxin; guanosine5′-3- O-(thio)triphosphate; phospholipase C; GI; Ca 2+/calmodulin-dependent protein kinase; TRPC4; Dendrite; gastrointestinal; Gi2; n.s; enhanced GFP; Galphai2; phosphatidylinositol 4,5-bisphosphate; not significant; GPCR; PIP2; guanosine5′-3-O-(thio)triphosphate; Ca(2+)/calmodulin-dependent protein kinase; PIP
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/j.ceca.2013.07.006

Abstract The ubiquitous transient receptor potential canonical (TRPC) channels function as non-selective, Ca2+ -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-Gαi2Q205L -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.