Thalmann R H
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
J Neurosci. 1988 Dec;8(12):4589-602. doi: 10.1523/JNEUROSCI.08-12-04589.1988.
These experiments show that a synaptic response in brain, namely, the late inhibitory postsynaptic potential (IPSP) of hippocampal CA3 neurons in the rat hippocampal slice, was blocked by 2 compounds affecting guanosine triphosphate (GTP)-binding proteins. The first of these compounds, pertussis toxin, an inactivator of several GTP-binding proteins (G-proteins), excluding the GTP-binding protein that stimulates adenylyl cyclase, was injected intrahippocampally. The second compound, GTP gamma S, a nonhydrolyzable analog of GTP, was injected directly into postsynaptic neurons via the recording electrode. An ADP-ribosylation assay verified that the pertussis toxin had modified a major portion of the hippocampal pertussis toxin substrates of approximately 40,000 apparent molecular weight. Each agent blocked the conductance associated with both the late IPSP and the response to baclofen, an agonist for a putative receptor mediating the late IPSP (GABAB). These compounds did not block the mossy fiber excitatory postsynaptic potential (EPSP), the GABAA-mediated early IPSP, or the response to the GABAA agonist 4,5,6,7-tetrahydroisoxazolo-(5,4-C)-pyridin-3-ol. It is possible that these measurements underestimated the degree of blockade of the specific potassium conductance of the late IPSP since at least a portion of the GTP-gamma S-insensitive response was not a potassium conductance at all. Rather, it was a response with a reversal potential some 30 mV positive to that of the late IPSP. On the basis of these experiments, I propose that the transmitter receptor of the late IPSP activates a potassium conductance via a G-protein that is sensitive to blockade by pertussis toxin and that GTP gamma S and baclofen activate a conductance that depends upon the same G-proteins and/or potassium channels as does the late IPSP.
这些实验表明，大脑中的一种突触反应，即大鼠海马切片中海马CA3神经元的晚期抑制性突触后电位（IPSP），被两种影响鸟苷三磷酸（GTP）结合蛋白的化合物所阻断。这些化合物中的第一种是百日咳毒素，它是几种GTP结合蛋白（G蛋白）的灭活剂，但不包括刺激腺苷酸环化酶的GTP结合蛋白，通过海马内注射。第二种化合物是GTPγS，它是一种不可水解的GTP类似物，通过记录电极直接注射到突触后神经元中。ADP核糖基化分析证实，百日咳毒素修饰了大约40000表观分子量的海马百日咳毒素底物的大部分。每种药物都阻断了与晚期IPSP以及对巴氯芬（一种介导晚期IPSP的假定受体的激动剂，GABAB）的反应相关的电导。这些化合物没有阻断苔藓纤维兴奋性突触后电位（EPSP）、GABAA介导的早期IPSP或对GABAA激动剂4,5,6,7-四氢异恶唑并（5,4-C）吡啶-3-醇的反应。由于至少一部分对GTPγS不敏感的反应根本不是钾电导，这些测量可能低估了晚期IPSP特异性钾电导的阻断程度。相反，它是一种反转电位比晚期IPSP正约30mV的反应。基于这些实验，我提出晚期IPSP的递质受体通过一种对百日咳毒素阻断敏感的G蛋白激活钾电导，并且GTPγS和巴氯芬激活一种电导，该电导依赖于与晚期IPSP相同的G蛋白和/或钾通道。
