title: TRPC6 inhibited NMDA current in cultured hippocampal neurons.
abstract: N-methyl-D-aspartate (NMDA) receptors play a key role in excitatory synaptic transmission, plasticity and neural development, and they also mediate excitotoxicity that is involved in both acute neuronal damage and chronic neurodegenerative diseases. Regulation of the NMDA channel activity is critical for the pathological processes of these diseases. The canonical transient receptor potential channels (TRPCs) are Ca(2+)-permeable nonselective cation channels with various physiological functions, including promoting neuronal survival. Here, we reported that TRPC6, a member of the TRPC family, inhibited the NMDA-induced current in primary cultured hippocampal neurons. Overexpression of TRPC6 or application of 1-oleoyl-2-acetyl-sn-glycerol, a compound known to activate TRPCs, inhibited the NMDA-induced current in these neurons assayed by the whole-cell patch-clamp recording. Consistently, downregulation of TRPC6 or application of SKF96365, a compound known to inhibit TRPCs, enhanced this current. The peak amplitude of the NMDA current in the neurons isolated from TRPC6 transgenic mice was greatly suppressed than that in the neurons isolated from the wild-type littermates. Furthermore, TRPC6 might activate calcineurin to inhibit the activity of NMDA receptors in cultured hippocampal neurons. Together, these results suggested that TRPC6 might be a novel negative modulator of NMDA receptors.
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration and Institute of Nautical Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, China. hmshen1971@gmail.com
authors.forename: Hongmei
authors.initials: H
authors.lastname: Shen
authors.forename: Jie
authors.initials: J
authors.lastname: Pan
authors.forename: Longlu
authors.initials: L
authors.lastname: Pan
authors.forename: Nianjiao
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D019703:Calcineurin / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects / Q000502:physiology; D004075:Diglycerides / Q000494:pharmacology; D015536:Down-Regulation; D017930:Genes, Reporter; D006624:Hippocampus / Q000166:cytology*; D007093:Imidazoles / Q000494:pharmacology; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050052:TRPC Cation Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000074287:TRPC6 Cation Channel; D014162:Transfection; D015854:Up-Regulation
chemical_list: C520323:1-oleoyl-2-acetoyl-sn-glycerol; D001426:Bacterial Proteins; D004075:Diglycerides; D007093:Imidazoles; D008164:Luminescent Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C492146:Trpc6 protein, mouse; C492145:Trpc6 protein, rat; C054562:yellow fluorescent protein, Bacteria; D016202:N-Methylaspartate; D019703:Calcineurin; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole