SEROTONIN-MEDIATED INHIBITORY POSTSYNAPTIC POTENTIAL IN GUINEA-PIG PREPOSITUS-HYPOGLOSSI AND FEEDBACK INHIBITION BY SEROTONIN
SEROTONIN-MEDIATED INHIBITORY POSTSYNAPTIC POTENTIAL IN GUINEA-PIG PREPOSITUS-HYPOGLOSSI AND FEEDBACK INHIBITION BY SEROTONIN
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DOI：
10.1113/jphysiol.1990.sp017994
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发表时间：
1990-03-01
影响因子：
5.5
通讯作者：
WILLIAMS, JT
中科院分区：
文献类型：
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作者：
BOBKER, DH;WILLIAMS, JT
1. 细胞内记录是由豚鼠大脑切片中舌前核 (PH) 的神经元进行的。局灶刺激诱发抑制性突触后电位 (IPSP)，其幅度通常为 10-25 mV，持续时间为 1 s。 IPSP 反转电位显示出对外部钾浓度 ([K+]o) 的能斯特依赖性。 2. Spiperone 阻断 IPSP，IC50 为 40 nM，而酮舍林和 (-)舒必利则没有效果。可卡因(1μM)使IPSP半持续时间延长157％，并使振幅增加28％。 3. 5-羟色胺（5-HT，血清素）超极化PH细胞，对照中的EC50为8.5μM，可卡因（10μM）中的EC50为135nM。 8-羟基-2-(二正丙氨基)-四氢萘 (8-OH-DPAT) 也使 PH 细胞超极化，EC50 为 16 nM，但最大效果仅为最大 5-HT 超极化的 81%。 Spiperone 使 5-HT 浓度反应曲线平行右移； Schild 分析给出的 Kd 为 10 nM。将 5-HT 施加到电压钳位在其静息电位（约 -55 mV）附近的神经元上，引起外向电流和膜电导增加。 4. 非超极化浓度的 5-HT 和 5-HT1 受体激动剂 1-(间三氟甲基苯基)哌嗪 (TFMPP) 和 1-(3-氯苯基)哌嗪 (mCPP) 可逆地降低 IPSP 的振幅。后两种化合物的IC50值分别为50nM和1.5μM；最大效果是90%的抑制。两种化合物均不影响膜电位，也不改变 5-HT 诱导的超极化。 Quipizine 竞争性拮抗 TFMPP，估计 Kd 为 165 nM。 5. 当施加一系列刺激时，在第一次刺激后观察到 IPSP 的抑制。频率为 1 Hz 时，抑制率约为 75%。 IPSP的这种频率依赖性“衰退”通过用TFMPP(1μM)预处理而显着减弱。 6. 结论：PH细胞中的IPSP是由5-HT作用于5-HT1A受体激活钾电导引起的。突触前 5-HT1D 受体的激活可以抑制 5-HT 的释放。这种突触前受体似乎至少部分负责这种耗尽现象，并且可能参与 5-HT 突触传递的生理调节。
1. Intracellular recordings were made from neurones of the nucleus prepositus hypoglossi (PH) in slices of guinea-pig brain. Focal stimulation evoked an inhibitory postsynaptic potential (IPSP) that was typically 10-25 mV in amplitude and 1 s in duration. The IPSP reversal potential showed a Nernstian dependence on the external potassium concentration ([K+]o). 2. Spiperone blocked the IPSP with an IC50 of 40 nM, while ketanserin and (-)sulpiride had no effect. Cocaine (1 .mu.M) prolonged the IPSP half-duration by 157%, and increased the amplitude by 28%. 3. 5-Hydroxytryptamine (5-HT, serotonin) hyperpolarized PH cells with an EC50 of 8.5 .mu.M in control, and 135 nM in cocaine (10 .mu.M). 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) also hyperpolarized PH cells with an EC50 of 16 nM, although the maximal effect was only 81% of the maximum 5-HT hyperpolarization. Spiperone produced a parallel, right shift of the 5-HT concentration-response curve; Schild analysis gave a Kd of 10 nM. Application of 5-HT to neurones voltage-clamped near their resting potential (about -55 mV) caused an outward current and an increase in membrane conductance. 4. The amplitude of the IPSP was reversibly decreased by non-hyperpolarizing concentrations of 5-HT and by the 5-HT1 receptor agonists 1-(m-trifluoromethylphenyl)piperazine (TFMPP) and 1-(3-chlorophenyl)piperazine (mCPP). The IC50 values for the latter two compounds were 50 nM and 1.5 .mu.M, respectively; the maximal effect was a 90% inhibition. Neither compound affected the membrane potential nor changed the hyperpolarization induced by 5-HT. Quipizine competitively antagonized TFMPP with an estimated Kd of 165 nM. 5. When trains of stimuli were applied, an inhibition of the IPSP was observed following the first stimulus. At a frequency of 1 Hz, the inhibition was approximately 75%. This frequency-dependent ''run-down'' of the IPSP was markedly attenuated by pre-treatment with TFMPP (1 .mu.M). 6. It is concluded that the IPSP in PH cells is caused by 5-HT acting on 5-HT1A receptors to activate a potassium conductance. The release of 5-HT can be inhibited by activation of a presynaptic 5-HT1D receptor. This presynaptic receptor appears to be at least partly responsible for the run-down phenomenon, and may be involved in the physiological regulation of 5-HT synaptic transmission.