title: Spatiotemporal and anatomical analyses of P2X receptor-mediated neuronal and glial processing of sensory signals in the rat dorsal horn.
abstract: Extracellularly released adenosine triphosphate (ATP) modulates sensory signaling in the spinal cord. We analyzed the spatiotemporal profiles of P2X receptor-mediated neuronal and glial processing of sensory signals and the distribution of P2X receptor subunits in the rat dorsal horn. Voltage imaging of spinal cord slices revealed that extracellularly applied ATP (5-500 μM), which was degraded to adenosine and acting on P1 receptors, inhibited depolarizing signals and that it also enhanced long-lasting slow depolarization, which was potentiated after ATP was washed out. This post-ATP rebound potentiation was mediated by P2X receptors and was more prominent in the deep than in the superficial layer. Patch clamp recording of neurons in the superficial layer revealed long-lasting enhancement of depolarization by ATP through P2X receptors during the slow repolarization phase at a single neuron level. This depolarization pattern was different from that in voltage imaging, which reflects both neuronal and glial activities. By immunohistochemistry, P2X(1) and P2X(3) subunits were detected in neuropils in the superficial layer. The P2X(5) subunit was found in neuronal somata. The P2X(6) subunit was widely expressed in neuropils in the whole gray matter except for the dorsal superficial layer. Astrocytes expressed the P2X(7) subunit. These findings indicate that extracellular ATP is degraded into adenosine and prevents overexcitation of the sensory system, and that ATP acts on pre- and partly on postsynaptic neuronal P2X receptors and enhances synaptic transmission, predominantly in the deep layer. Astrocytes are involved in sensitization of sensory network activity more importantly in the superficial than in the deep layer.
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan Department of Medicine, Keio University Tsukigase Rehabilitation Center, 380-2 Tsukigase, Izu City, Shizuoka 410-3215, Japan Department of Anatomy and Morphological Neuroscience, Shimane University School of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan Department of Neuroscience, School of Medicine, Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan.
authors.forename: Ryoma
authors.initials: R
authors.lastname: Aoyama
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Okada
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Yokota
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.forename: Kentaro
authors.initials: K
authors.lastname: Fukuda
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Shinozaki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chiba
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Yasui
authors.forename: Fusao
authors.initials: F
authors.lastname: Kato
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000235:genetics / Q000502:physiology; D005260:Female; D008297:Male; D009457:Neuroglia / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D020671:Posterior Horn Cells / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis / Q000502:physiology*; D058474:Receptors, Purinergic P2X1 / Q000096:biosynthesis / Q000502:physiology*; D058477:Receptors, Purinergic P2X3 / Q000096:biosynthesis / Q000502:physiology*; D058485:Receptors, Purinergic P2X5 / Q000096:biosynthesis / Q000502:physiology*; D058486:Receptors, Purinergic P2X7 / Q000096:biosynthesis / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000737:chemistry / Q000502:physiology*; D013116:Spinal Cord / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D013997:Time Factors
chemical_list: D018048:Receptors, Purinergic P2; D058474:Receptors, Purinergic P2X1; D058477:Receptors, Purinergic P2X3; D058485:Receptors, Purinergic P2X5; D058486:Receptors, Purinergic P2X7; C110590:purinoceptor P2X6