title: Substance P Activates Ca2+-Permeable Nonselective Cation Channels through a Phosphatidylcholine-Specific Phospholipase C Signaling Pathway in nNOS-Expressing GABAergic Neurons in Visual Cortex.
abstract: To understand the functions of the neocortex, it is essential to characterize the properties of neurons constituting cortical circuits. Here, we focused on a distinct group of GABAergic neurons that are defined by a specific colocalization of intense labeling for both neuronal nitric oxide synthase (nNOS) and substance P (SP) receptor [neurokinin 1 (NK1) receptors]. We investigated the mechanisms of the SP actions on these neurons in visual cortical slices obtained from young glutamate decarboxylase 67-green fluorescent protein knock-in mice. Bath application of SP induced a nonselective cation current leading to depolarization that was inhibited by the NK1 antagonists in nNOS-immunopositive neurons. Ruthenium red and La(3+), transient receptor potential (TRP) channel blockers, suppressed the SP-induced current. The SP-induced current was mediated by G proteins and suppressed by D609, an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), but not by inhibitors of phosphatidylinositol-specific PLC, adenylate cyclase or Src tyrosine kinases. Ca(2+) imaging experiments under voltage clamp showed that SP induced a rise in intracellular Ca(2+) that was abolished by removal of extracellular Ca(2+) but not by depletion of intracellular Ca(2+) stores. These results suggest that SP regulates nNOS neurons by activating TRP-like Ca(2+)-permeable nonselective cation channels through a PC-PLC-dependent signaling pathway.
authors.affiliation: Department of Neuroscience, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Endo
authors.affiliation: Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine and JST, CREST, Maebashi 371-8511, Japan.
authors.forename: Yuchio
authors.initials: Y
authors.lastname: Yanagawa
authors.affiliation: Department of Neuroscience, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Komatsu
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects* / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D054833:Isoindoles / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism*; D014793:Visual Cortex / Q000166:cytology*
chemical_list: C112297:10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; D000873:Anthracenes; D001896:Boron Compounds; D002121:Calcium Channel Blockers; D018683:Excitatory Amino Acid Agents; D007093:Imidazoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011804:Quinolines; D011812:Quinuclidines; C109112:SB 222200; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; C085215:SR 140333; D013373:Substance P; C109986:2-aminoethoxydiphenyl borate; D052250:Nitric Oxide Synthase Type III; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium
keywords: NK1 receptor; PC-PLC; neuronal nitric oxide synthase; slice; tachykinin