PENTOBARBITAL PHARMACOLOGY OF MAMMALIAN CENTRAL NEURONS GROWN IN TISSUE-CULTURE
PENTOBARBITAL PHARMACOLOGY OF MAMMALIAN CENTRAL NEURONS GROWN IN TISSUE-CULTURE
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DOI：
10.1113/jphysiol.1978.sp012388
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发表时间：
1978-01-01
影响因子：
5.5
通讯作者：
RANSOM, BR
中科院分区：
文献类型：
--
作者：
BARKER, JL;RANSOM, BR
采用细胞内记录结合水浴应用、细胞外离子电泳或局灶扩散技术，研究了巴比妥类麻醉剂戊巴比妥对组织培养的小鼠中枢神经系统神经元的膜特性和氨基酸药理学的影响。在洗浴介质中加入麻醉浓度的戊巴比妥，可消除所有自发性突触活动，但不会使单个细胞电不可兴奋，也不会阻止诱发的突触活动。戊巴比妥的局部离子电泳或钝头微量移液管的扩散可逆地增加了膜电导，有效地抑制兴奋性，而不直接影响个体动作电位特征。戊巴比妥诱导的膜电导可逆地阻断印防己毒素。戊巴比妥电压响应的反转电位依赖于Cl-梯度，与GABA相似。戊巴比妥可逆地增强了GABA产生的电导增加与可变的响应动力学减慢，GABA剂量-响应曲线向左移动。对甘氨酸和β的反应-丙氨酸不受影响。戊巴比妥的高离子电泳电流，可测量地增加膜电导，衰减和显着减缓GABA的反应。通过将GABA脉冲叠加在低水平GABA电流上，观察到对GABA反应的类似影响。戊巴比妥，在膜电导增加的情况下，可逆地抑制去极化反应谷氨酸，而不改变反应动力学。与膜电导明显降低相关的对乙酰胆碱的缓慢反应不受药物的影响。双倒数图数据的分析表明戊巴比妥和谷氨酸之间的非竞争性拮抗作用。戊巴比妥抑制谷氨酸不受印防己毒素。GABA和谷氨酸反应似乎对戊巴比妥同样敏感。药物与氨基酸受体偶联事件的特异性相互作用由戊巴比妥移液器放置靠近氨基酸反应位点的要求指示。戊巴比妥可通过直接激活突触后GABA受体偶联的Cl-传导、增强突触后GABA诱导的传导事件（可能在GABA受体水平）和抑制突触后谷氨酸诱导的兴奋（可能在传导机制水平）来抑制神经元兴奋性。
The effects of the barbiturate anesthetic pentobarbitone on the membrane properties and amino acid pharmacology of mouse CNS neurons grown in tissue culture were studied using intracellular recording coupled with bath application, extracellular ionophoresis or focal diffusion. The addition of an anesthetic concentration of pentobarbitone to the bathing medium abolished all spontaneous synaptic activity, but did not render individual cells electrically inexcitable nor prevent evoked synaptic activity. Focal ionophoresis of pentobarbitone or diffusion from blunt micropipettes reversibly increased membrane conductance, effectively dampening excitability without directly affecting individual action potential characteristics. Pentobarbitone-induced membrane conductance was reversibly blocked by picrotoxin. The inversion potential of the pentobarbitone voltage response depended on Cl- gradients and was similar to that of GABA. Pentobarbitone reversibly enhanced the conductance increase produced by GABA with a variable slowing of response kinetics, shifting GABA dose-response curves to the left. Responses to glycine and .beta.-alanine were not affected. Higher ionophoretic currents of pentobarbitone, which measurably increased membrane conductance, attenuated and markedly slowed GABA responses. Similar effects on GABA responses were observed by superimposing GABA pulses on low level GABA currents. Pentobarbitone, in the absence of an increase in membrane conductance, reversibly depressed depolarizing responses to glutamate without changing response kinetics. Slower responses to acetylcholine which were associated with an apparent decrease in membrane conductance were not affected by the drug. Analysis of double-reciprocal plot data suggested a non-competitive type of antagonism between pentobarbitone and glutamate. Pentobarbitone depression of glutamate was not affected by picrotoxin. Both GABA and glutamate responses appeared to be equally sensitive to pentobarbitone. Specific interaction of the drug with amino acid receptor-coupled events is indicated by the requirement for pentobarbitone pipette placement close to the amino acid response site. Pentobarbitone may depress neuronal excitability by directly activating post-synaptic GABA-receptor coupled Cl- conductance, potentiating post-synaptic GABA-induced conductance events, probably at the level of the GABA receptor and depressing post-synaptic glutamate-induced excitation, probably at the level of the conductance mechanism.