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Novel tetrodotoxin-sensitive Ca^<2+> current in mammalian neurons - function and distribution

Research Project

Project/Area Number 02404022
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Neurophysiology and muscle physiology
Research InstitutionTohoku University

Principal Investigator

AKAIKE Norio  Tohoku Univ. Sch. Med. Professor, 医学部, 教授 (30040182)

Co-Investigator(Kenkyū-buntansha) TOKUTOMI Naofumi  Tohoku Univ. Sch. Med. Assistant Professor, 医学部, 助手 (30227582)
NAKAYE Toshio  Tohoku Univ. Sch. Med. Assistant Professor, 医学部, 助手 (20155659)
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1991: ¥6,300,000 (Direct Cost: ¥6,300,000)
Keywordsrat hippocampal CA1 region / isolated pyramidal neuron / tetrodotoxin-sensitive Ca current / divalent cation permeability / scorpion toxin / heterogeneous distribution / kinetics / lidocaine / ラット / 海馬CA1領域 / TTX感受性Ca電流 / 単離錐体細胞 / 電気生理学
Research Abstract

1. Voltage-dependent Ca^<2+> currents (I_<Ca>s) in neurons can be classified into T-, N-and L-types. In the CA1 pyramidal neurons freshly dissociated from rat hippocampus we found an additional tetrodotoxin (TTX) -sensitive Ca^<2+> current (termed 'TTX-I_<Ca>'). The TTX-I_<Ca> showed a heterogeneous distribution, preferentially in the dorsal site of CA1 region.
2. Activation and inactivation processes of the TTX-I_<Ca> were highly potential-dependent, and the latter was fitted by a double exponential function. The TTX-I_<Ca> was activated at a threshold potential of about-55 mV and reached full activation at-30 mV. The steady-state inactivation of TTX-I_<Ca> could be fitted by a Boltzmann equation with slope factor of 6.0 mV and a half-inactivation voltage of-72.5 mV.
3. When the peak amplitudes of TTX-I_<Ca> were plotted as a function of extracellular Ca^<2+> concentration ([Ca^<2+>]_o), the current amplitude increased linearly without showing any saturation.
4. The ratio of peak amplitude in the individual I-V relationships of Ca^<2+>, Si^<2+> and Ba^<2+> currents passing through the TTX-sensitive Ca^<2+>-conducting channel was 1 : 0.33 : 0.05, although the current kinetics were much the same.
5. TTX inhibited the TTX-I_<Ca> in time and concentration-dependent manner without affecting the current kietics. Lignocaine inhibited the TTX-I_<Ca> in a second in a concentration-dependent manner, with accelerating the inactivation process. The concentrations of half-inhibition (IC_<50>) were 3.5x10^<-9>M for TTX and 3.6x10^<-4>M for lignocaine.
6. Scorpion toxin prolonged the inactivation phase of TTX-I_<Ca> in a time-and concentration-dependent manner. In the toxin-treated neurons, both the slow time constant of inactivation (tau_<is>) and its functional contribution to the total current increased with increasing the toxin concentration.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Akaike,N.,Takahashi,K.& Morimoto,M.: "Heterogeneous distribution of tetrodotoxin-sensitive calcium conducting channels in rat hippocampal CA1 neurons." Brain Res.556. 135-138 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shirasaki,T.,Harata,N.Nakaye,T.& Akaike,N.: "Interaction of various non-steroidal anti-inflammatories and quinolone antimicrobials on GABA response in rat dissociated hippocampal pyramidal neurons." Brain Res.562. 329-331 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shirasaki,T.,Harata,N.,Nakaye,T.,Akaike,N.: "Quinolones do not interact with NMDA receptor in dissociated rat hippocampal neurons." Brain Res.562. 344-346 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ueno,S.,Nakaye,T.& Akaike,N.: "Proton-induced sodium current in freshly dissociated hypothalamic neurones of the rat." J.Physiol.(1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Akaike,N.& Takahashi,K.: "Tetrodxin-sensitive calcium-conduction channels in the rat hippocampal CA1 region." J.Physiol.(1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yamashita,y.,Akaike,N.Wakamori,M.,Ikeda,I.& Ogawa,H.: "Voltage-dependent current in isolated single merkel cells of rats." J.Physiol.(1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Akaike, N., takahashi, K. & Morimoto, M.: "Heterogeneous distribution of tetrodotoxin-sensitive calcium-conducting channels rat hippocampal CA1 neurons." Brain Res.556. 135-138 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Aibara, K. & Akaike, N.: "Acetylcholine-activated ionic currents in isolated paratracheal ganglion cells of the rat." BRain Res.558. 20-26 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shirasaki, T., Klee, M. R., Nakaye, T & Akaike, N.: "Differential blockade of bicuculline and strychnine on GABA- and glycine-induced responses in dissociated rat hippocampal pyramidal cells." BRain Res.561. 77-83 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shirasaki, T., Harata, N., Nakaye, T. & Akaike, N.: "Interaction of various non-steroidal anti-inflammatories and quinolone antimicrobials on GABA response in rat dissociated hippocampal pyramidal neurons." BRain Res.562. 329-331 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shirasaki, T., Harata, N., Nakaye, T. & Akaike, N.: "Quinolones do not interact with NMDA receptor in dissociated rat hippocampal neurons." Brain Res.562. 344-346 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Harata, N., Tateishi, N. & Akaike, N.: "Acetylcholine receptors in dissociated nucleus basalis of Meynert neurons of the rat." Neurosci. Lett.130. 153-156 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Akaike, N., Harata, N. & Tateishi, N.: "Modulatory action of cholinergic drugs on N-methyl-D-aspartate response in dissociated rat nucleus basalis of meynert neurons." Neurosci. Lett.130. 243-247 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yakushiji, T., Shirasaki, T. & Akaike, N.: "Non-competitive inhibition of GABA_A responses by a new class of quinolones and non-steroidal anti-inflammatories in dissociated frog sensory neurones." Br. J. Pharmacol.105. 13-18 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Akaike, N., Harata, N., Ueno, S. & Tateishi, N.: "GABAergic synaptic current in dissociated nucleus basalis of Meynert neurons of the rat." Brain Res.570. 102-108 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Furukawa, K., Akaike, N., Onodera, H. & Kogure, K.: "Expression of 5-HT_3 receptors in PC12 cells treated with NGF and 8-Br-cAMP." J. Neurophysiol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Itabashi, S., Aibara, K., Sasaki, H. & Akaike, N.: "gamma-aminobutyric acid-induced response in rat dissociated paratracheal ganglion cells." J. Neurophysiol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shirasaki, T., Aibara, K. & Akaike, N.: "Direct modulation of affinity of GABA_A receptor by intracellular ATP in dissociated nucleus tractus solitarii neurons of rat." J. Physiol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ueno, S., Nakaye, T. & Akaike, N.: "Proton-induced sodium current in freshly dissociated hypothalamic neurons of the rat." J. Physiol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Akaike, N. & Takahashi, K.: "Tetrodoxin-sensitive calcium-conduction channels in the rat hippocampal CA1 region." J. Physiol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Yamashita. Y., Akaike, N., Wakamori, M. Ikeda, I. & Ogawa, H.: "Voltage-dependent currents in isolated single merkel cells of rats." J. Physiol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Akaike,N.Takahashi,K.&Morimoto,M.: "Heterogeneous distribution of tetrodotoxinーsensitive calciumconducting channels in rat hippocampal CA1 neurons." Brain Res.556. 135-138 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Shirasaki,T.Harata,N.,Nakaye,T.&Akaike,N.: "Interaction of various nonーsteroidal antiーinflammatories and quinolone antimicrobials on GABA response in rat dissociated hippocampal pyramidal neurons." Brain Res.562. 329-331 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Shirasaki,T.,Harata,N.,Nakaye,T.,Akaike,N.: "Q__〜uinolones do not interact with NMDA receptor in dissociated rat hippocampal neurons." Brain Res.562. 344-346 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ueno,S.,Nakaye,T.&Akaike,N.: "Protonーinduced sodium current in freshly dissociated hypothalamic neurones of the rat." J.Physiol.(1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Akaike,N.&Takahashi,K.: "Tetrodoxinーsensitive calciumーconduction channels in the rat hippocampal CA1 region." J.Physiol.(1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yamashita,Y.,Akaike,N.,Wakamori,M.,Ikeda,I.&Oaawa,H.: "Voltageーdependent current in isolated single merkel cells of rats." J.Physiol.(1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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