Terakado Masanori
Department of Pharmacology, Nihon University School of Dentistry.
J Oral Sci. 2014 Mar;56(1):49-57. doi: 10.2334/josnusd.56.49.
The α1-adrenoceptor agonist phenylephrine and the β-adrenoceptor agonist isoproterenol have opposite effects on evoked EPSPs (eEPSPs) in the cerebral cortex. The suppressive effects of phenylephrine on eEPSPs are mediated by modulation of postsynaptic glutamate receptors, whereas enhancement of eEPSPs by isoproterenol is due to facilitation of glutamate release from presynaptic terminals. The present study used whole-cell patch-clamp recordings from layer V pyramidal neurons in visuocortical slice preparations to assess the effects of phenylephrine and isoproterenol on the release probability of γ-aminobutyric acid (GABA). The present study recorded evoked inhibitory postsynaptic potentials (eIPSCs) by repetitive electrical stimulation (duration, 100 μs; 10 stimuli at 33 Hz) and miniature IPSCs (mIPSCs). The effects of phenylephrine (100 μM) depended on the amplitude of eIPSCs: phenylephrine decreased the paired-pulse ratios (PPRs) of eIPSCs with smaller amplitudes (<600 pA) but increased PPRs of eIPSCs with larger amplitude. Phenylephrine also exhibited amplitude-dependent modulation of mIPSCs, i.e., an increase in the frequency of smaller mIPSC events (<20 pA) and a decrease in the frequency of larger events. These findings suggest that α1-adrenoceptor activation facilitates GABA release from a subpopulation of GABAergic terminals that induce smaller-amplitude IPSCs in postsynaptic neurons. In contrast, isoproterenol (100 μM) consistently decreased the PPR of eIPSCs and increased the frequency of mIPSCs, suggesting that presynaptic β-adrenoceptors increase release probability from most GABAergic terminals. The complexity of adrenoceptor modulations in GABAergic synaptic transmission by α1-adrenoceptor and β-adrenoceptor activation may be due to the presence of pleiotropic subtypes of GABAergic interneurons in the cerebral cortex.
α1肾上腺素能受体激动剂去氧肾上腺素和β肾上腺素能受体激动剂异丙肾上腺素对大脑皮质诱发的兴奋性突触后电位（eEPSPs）具有相反的作用。去氧肾上腺素对eEPSPs的抑制作用是通过调节突触后谷氨酸受体介导的，而异丙肾上腺素增强eEPSPs则是由于促进了突触前终末谷氨酸的释放。本研究采用全细胞膜片钳记录视皮质切片制备中第V层锥体神经元的电活动，以评估去氧肾上腺素和异丙肾上腺素对γ-氨基丁酸（GABA）释放概率的影响。本研究通过重复电刺激（持续时间100 μs；33 Hz的10次刺激）记录诱发抑制性突触后电位（eIPSCs）和微小抑制性突触后电位（mIPSCs）。去氧肾上腺素（100 μM）的作用取决于eIPSCs的幅度：去氧肾上腺素降低了幅度较小（<600 pA）的eIPSCs的配对脉冲比率（PPRs），但增加了幅度较大的eIPSCs的PPRs。去氧肾上腺素还表现出对mIPSCs的幅度依赖性调节，即较小mIPSC事件（<20 pA）的频率增加，而较大事件的频率降低。这些发现表明，α1肾上腺素能受体激活促进了GABA能终末亚群释放GABA，这些终末在突触后神经元中诱发幅度较小的IPSCs。相反，异丙肾上腺素（100 μM）持续降低eIPSCs的PPR并增加mIPSCs的频率，表明突触前β肾上腺素能受体增加了大多数GABA能终末的释放概率。α1肾上腺素能受体和β肾上腺素能受体激活对GABA能突触传递中肾上腺素能受体调节的复杂性可能是由于大脑皮质中GABA能中间神经元存在多效性亚型。
