CHARACTERIZATION AND IONIC BASIS OF GABA-INDUCED DEPOLARIZATIONS RECORDED INVITRO FROM CAT PRIMARY AFFERENT NEURONS

CHARACTERIZATION AND IONIC BASIS OF GABA-INDUCED DEPOLARIZATIONS RECORDED INVITRO FROM CAT PRIMARY AFFERENT NEURONS
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DOI:
10.1113/jphysiol.1978.sp012189
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发表时间:
1978-01-01
影响因子:
5.5
通讯作者:
NISHI, S
NISHI, S
中科院分区:
医学1区
文献类型:
--
作者:
GALLAGHER, JP;HIGASHI, H;NISHI, S

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用细胞内微电极记录分离的猫脊神经节单个细胞对GABA灌流或离子导入的反应。在所研究的12种结构相关的化合物中,GABA在产生细胞膜去极化的能力方面是最有效的。确定浓度-反应关系的研究表明,需要2-3个GABA分子与GABA受体结合才能激活。荷包牡丹碱和印防己毒素均以非竞争性方式拮抗GABA诱导的膜电流。离子电泳法诱导的GABA去极化的平衡电势为-23.5.+-。6.1 mV。细胞内注入20种阴离子(Br-、I-、NO2-、NO3-、ClO4-、SCN-、Br4-、HS-、OCN-、ClO3-、BrO3-、F-、HCO2-、HSO3-、HCO3-、CH3CO2-、SO42-、C6H5O73-),表明激活的GABA受体膜对水化直径不超过ClO-的阴离子具有通透性。注入氯离子增强后,GABA去极化恢复到其对照水平的平均时间常数为27.8±-。2.6分钟。印防己毒素不会改变这个值。在灌流液中用外源阴离子交换氯离子时,10个小于或等于ClO_3~-的阴离子可使GABA去极化降低50~90%,使去极化时间延长1.5~2.0倍。控制力。唯一有一个小半径的例外是BR,它使幅度增加了10%-30%。10个大于ClO_3-的阴离子产生了双相效应,即,最初的增强,然后是显著的(高达100%)抑制反应。用CH3COO-、CH3SO4-或HOCH2CH2SO3-进行的实验表明,这种抑制是非竞争性的。
Responses of single cells in the isolated cat spinal ganglion to GABA applied by superfusion or iontophoresis were recorded using intracellular microelectrodes. Of the 12 structurally related compounds investigated, GABA was the most effective in its ability to produce a depolarization of the cell membrane. Studies determining concentration-response relationships indicated that 2-3 molecules of GABA are required to combine with the GABA receptor for activation. Bicuculline and picrotoxin each acted in a non-competitive manner to antagonize the GABA-induced membrane current. The equilibrium potential for iontophoretically induced GABA depolarizations (EGABA) was -23.5 .+-. 6.1 mV. EGABA was dependent on [Cl-]o [extracelluar concentration of Cl-], but independent of [Na+]o, [K+]o, or [Ca2+]o. Intracellular injection of 20 anions (Br-, I-, NO2-, NO3-, ClO4-, SCN-, BR4-, HS-, OCN-, ClO3-, BrO3-, F-, HCO2-, HSO3-, HCO3-, CH3CO2-, SO42-, C6H5O73-), indicated that the activated GABA receptor membrane was permeable to those anions whose hydrated diameter is no longer than that of ClO3-. Restoration of the GABA depolarization to its control level after augmentation by Cl- injection had a mean time constant of 27.8 .+-. 2.6 min. Picrotoxin did not alter this value. When foreign anions were exchanged for Cl- in the perfusion solution, the 10 anions smaller or equal to ClO3- decreased the GABA depolarization by 50-90% and increased its time course 1.5-2.0 .times. control. The only exception having a small radius was Br- which augmented the amplitude 10-30%. The 10 anions larger than ClO3- produced a biphasic effect, i.e., an initial augmentation followed by a marked (up to 100%) depression of the response. Experiments with CH3COO-, CH3SO4-, or HOCH2CH2SO3- indicated that this depression was non-competitive.