1989 Fiscal Year Final Research Report Summary
Macro- and microscopic analysis of glycine-gated response in isolated CNS neurons.
| Project/Area Number |
63480107
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurophysiology and muscle physiology
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| Research Institution | TOHOKU UNIVERSITY (1989)
Kyushu University (1988) |
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Principal Investigator |
AKAIKE Norio Tohoku University School of Medicine, Professor, 医学部, 教授 (30040182)
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| Co-Investigator(Kenkyū-buntansha) |
OYAMA Yasuo Tohoku University School of Medicine, Assistant Researcher, 医学部, 助手 (80214229)
NAKAYE Toshio Tohoku University School of Medicine, Assistant Researcher, 医学部, 助手 (20155659)
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| Project Period (FY) |
1988 – 1989
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| Keywords | rat / hypothalamus / isolated neuron / glycine / Cl^- response / strychnine / NMDA / T-type Ca channel |
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| Research Abstract |
Pharmacological properties and kinetics of glycine-induced currents were investigated in single ventromedial hypothalamic (VMH) neurons acutely isolated from young and adult rats by the use of a 'concentration-clamp' technique, which allows both internal perfusion and rapid application of an external solution under single-electrode voltage-clamp. The glycine-induced current reversed at the Cl^- equilibrium potential (E_<Cl>), and a ten-fold change of extracellular Cl^- concentration resulted in a 53 mV shift of the glycine reversal potential. Glycine-induced Cl^- currents increased sigmoidally in a concentration-dependent manner with a K_d of 9 x 10^<-5> M at the Hill coefficient of 1.8. The glycine-induced conductance exhibited a striking voltage dependency at membrane potentials more negative than -50 mV and reached a steady state value when hyperpolarized beyond -110 mV. Both the activation and inactivation phases of glycine-induced response are described by double exponential funct
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ions (fast and slow components, respectively) with the concentrations used. All four time constants decreased with increasing glycine concentration. The blockade of the glycine response by strychnine and picrotoxin was noncompetitive. The responses to individual alpha- and (bata-amino acids were selectively antagonized by strychnine, but were not affected by bicuculline or a taurine antagonist, TAG, suggesting that alpha-and beta-amino acids activate the same glycine receptor. The pharmacological properties of low-threshold (T-type) Ca channels of VMH neurons for organic Ca blockers differed from those of peripheral ganglion cells and cultured neurons. The GABA-induced Cl^- current in rat isolated Purkinje cells was also investigated by concentration-clamp technique. The pharmacological property of GABA receptor was basically similar to that previously reported in other preparations. In isolated nucleus tructus solitarii neurons, glycine initiates the activation of NMDA receptors rather than that glycine prevents the desensitivation at NMDA receptors in the cells. Less
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