解剖学第二講座

《研究概要》

原　　著 1
　　　Spontaneous transient outward currents have been found in peripheral neurons and smooth muscle cells, but rarely in central neurons. Using a nystatin-perforated patch clamp technique, we succeeded in recording spontaneous transient outward currents in mouse dentate gyrus granule cells. Nociceptin/orphanin FQ increased the amplitude and frequency of transient outward currents. We consider modulation of spontaneous transient outward currents to be a new means to regulate cell activity in central neurons, and studied their characteristics and mechanism of augmentation. The whole-cell current-voltage relationship showed outward rectification and the reversal potential was close to the equilibrium potential for K+. The frequency of spontaneous transient outward currents increased at depolarized potentials. Tetraethylammonium, iberiotoxin and a Ca2+ chelator BAPTA-AM inhibited spontaneous transient outward currents. These results suggest the involvement of large-conductance Ca2+-activated K+ channels. Single-channel recordings in the inside-out configuration revealed Ca2+-activated K+ channels with a conductance ranging from 82 to 352 pS. The augmenting effect of nociceptin/orphanin FQ was cancelled by [Phe1Ψ(CH2-NH)Gly2]Nociceptin(1-13)NH2. Cd2+ did not affect the transient outward currents or augmentation by nociceptin/orphanin FQ. Whereas nociceptin/orphanin FQ, theophylline and cyclic ADP-ribose induced transient outward currents with short duration observed under control conditions, inositol 1, 4, 5-trisphosphate induced transient outward currents with long duration, in addition to those with short duration. Ryanodine inhibited nociceptin/orphanin FQ from augmenting spontaneous transient outward currents. Our data suggest that Ca2+ sparks transiently activate large-conductance Ca2+-activated K+ channels to induce transient outward currents. Nociceptin/orphanin FQ probably sensitizes ryanodine receptors and increases transient outward currents to reduce cell excitability.
原　　著 2
　　　Nociceptin peptide-receptor system is known to be essential for the regulation of hearing ability. The mRNA for nociceptin precursor protein is highly expressed in the brainstem. We explored a detailed hybridohistochemical expression pattern of the nociceptin precursor mRNA in the mouse brainstem, and identified positive cells in several auditory brainstem nuclei. Positive cells were seen in the dorsal and ventral nuclei of the lateral lemniscus, the rostral periolivary region, the lateroventral and medioventral periolivary nuclei, the dorsal periolivary region, the superior paraolivary nucleus, and the external cortex and dorsal cortex of the inferior colliculus. Of these, the medioventral and lateroventral periolivary nuclei, the major sites of origin of the olivocochlear bundle, were most populated by positive cells.

《研究業績》
原　　著
  1. Shirasaki T, Houtani T, Sugimoto T and Matsuda H (2001)
    Spontaneous transient outward currents: modulation by nociceptin in murine dentate gyrus granule cells.
    Brain Res 917: 191-205

  2. Kakimoto S, Houtani T, Sato K, Ueyama T, Sakuma S, Munemoto Y, Ohishi H, Kase M, Yamashita T, Takeshima H and Sugimoto T (2001)
    Brainstem auditory regions in mice: expression of nociceptin/orphanin FQ precursor mRNA in select neurons.
    Neurosci Lett 314: 37-40

学会発表

  1. 宝谷剛志，杉本哲夫（２００1）
    新規イオンチャネル型受容体の探索．
    第２４回日本神経科学・第４４回日本神経化学合同大会，京都

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