PHARMACOLOGICAL EVIDENCE FOR 2 KINDS OF GABA RECEPTOR ON RAT HIPPOCAMPAL PYRAMIDAL CELLS STUDIED INVITRO
PHARMACOLOGICAL EVIDENCE FOR 2 KINDS OF GABA RECEPTOR ON RAT HIPPOCAMPAL PYRAMIDAL CELLS STUDIED INVITRO
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DOI：
10.1113/jphysiol.1982.sp014256
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发表时间：
1982-01-01
影响因子：
5.5
通讯作者：
NICOLL, RA
中科院分区：
文献类型：
--
作者：
ALGER, BE;NICOLL, RA
用大鼠海马脑片制备法，结合细胞内记录和离子电泳技术，研究了GABA对海马CA 1区锥体细胞的作用。GABA在索马引起超极化（H）反应。这种H反应的逆转电位与刺激锥体细胞轴突诱发的抑制性突触后电位（IPSP）相同。GABA作用于顶树突时，主要引起去极化（D）反应，但也可引起H反应，GABA拮抗剂甲碘荷包牡丹碱、印防己毒素、青霉素和戊四唑对D反应的作用均比对H反应强10-100倍。当这些药物的中间剂量阻断D反应时，超极化反应在树突中未被发现。GABA类似物4，5，6，7-四氢异恶唑并[5，4-c]吡啶-3-醇（THIP）可优先激活其他系统中的突触受体，在树突中激发H反应。它在诱发D反应方面的效力是GABA的1/7。戊巴比妥对D反应的增强程度远大于对H反应的增强程度，而地西泮对H反应的增强程度更大。尼泊金酸，低温和低Na+介质都增加了D响应的大小，离子导入应用GABA，表明一个积极的摄取过程限制了它们的大小。H反应可能反映了突触受体的激活，这些受体高度集中在锥体细胞胞体起始段上，但也存在于树突上。树突中诱发的去极化反应反映了突触外受体的激活。显然，通常无法检测到的突触释放的GABA量可以溢出到突触外（D）受体上。D受体活化可在戊巴比妥存在下检测到。溢出显着增强在亚生理温度下，大概是由于增强释放GABA和GABA摄取系统的损害。
The rat hippocampal slice preparation was used in conjunction with intracellular recording and ionophoresis to study the action of GABA on CA1 pyramidal cells. GABA elicits a hyperpolarizing (H) response at the soma. The reversal potential of this H response is the same as for inhibitory postsynaptic potentials (IPSP) evoked by stimulating pyramidal cell axons. GABA elicits primarily depolarizing (D) responses when applied to the apical dendrites, but H responses can also be found. The GABA antagonists, bicuculline methiodide, picrotoxin, penicillin and pentylenetetrazole are all 10-100 times more potent on the D response than on the H response. Hyperpolarizing responses are uncovered in the dendrites when intermediate doses of these drugs block the D response. The GABA analog 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridine-3-ol (THIP), which may activate synaptic receptors preferentially in other systems, elicits H responses in the dendrites. It is 1/7 as potent as GABA in eliciting D responses. Pentobarbitone enhances D responses to a much greater extent than H responses, while diazepam enhances H responses to a greater extent. Nipecotic acid, low temperture and low Na+ media all increase the size of D responses to ionophoretically applied GABA, indicating that an active uptake process limits their size. H responses may reflect the activation of synaptic receptors, which are highly concentrated on the pyramidal cell soma-initial segment but are also present on the dendrities. Depolarizing responses which are evoked in the dendrites reflect the activation of extrasynaptic receptors. Evidently, an ordinarily undetectable amount of synaptically released GABA can spill over onto extrasynaptic (D) receptors. D receptor activation can be detected in the presence of pentobarbitone. Spillover is markedly enhanced at subphysiological temperatures, presumably due to enhanced release of GABA and impairment of the GABA-uptake system.