Yakel J L, Trussell L O, Jackson M B
Department of Biology, University of California, Los Angeles 90024.
J Neurosci. 1988 Apr;8(4):1273-85. doi: 10.1523/JNEUROSCI.08-04-01273.1988.
Serotonin (5-HT) produced 3 different types of responses in neurons of mouse hippocampal and striatal cell cultures. These 3 responses have been characterized in terms of their pharmacological specificity, physiological mechanism, and dependence on cytoplasmic components. The most frequently observed response was inhibitory and was the result of a receptor-mediated activation of an inwardly rectifying potassium conductance. Typically, the response peaked within 1-3 sec of agonist application and did not exhibit desensitization. 5-Methoxy-N,N-dimethyltryptamine also produced this response in both striatal and hippocampal cultures and had no effect on the other 5-HT currents observed in this study. The selective 5-HT agonists--8-hydroxy-2-(di-n-propylamino)-tetralin, 1-(m-chlorophenyl) piperazine, and 1-(2-methoxyphenyl) piperazine--did not activate this outward current response. Methysergide did not block the 5-HT-activated outward current and often acted as an agonist. The response was lost in low-series-resistance recordings which facilitate solution exchange between the patch electrode and the cell. The loss of this response was prevented by using high-resistance patch electrodes, which retard this exchange. The 2 other responses described in this study were excitatory. They were seen less often than the inhibitory response. One of the excitatory responses was fast, with a time to peak of approximately 200 msec and a duration of 2-4 sec. The other was slow, with a time to peak of 7-10 sec and a duration of approximately 30-40 sec. Both of these responses were accompanied by a conductance increase. The fast excitatory response reversed at depolarized potentials and desensitized with a rate that varied with voltage. Metoclopramide and d-tubocurarine completely and reversibly blocked this fast excitatory response, while methysergide had no effect. The fast excitatory response was not lost during intracellular dialysis of cells in cultures from either striatum or hippocampus. In cultures from both brain regions, the slow excitatory response was blocked by methysergide. The slow excitatory response was lost even in patch-clamp recordings with high-resistance electrodes. This response was similar to responses to dopamine, norepinephrine, and forskolin, all of which are known to activate adenylate cyclase in the CNS.
血清素（5-羟色胺，5-HT）在小鼠海马体和纹状体细胞培养的神经元中产生了3种不同类型的反应。这3种反应已根据其药理学特异性、生理机制以及对细胞质成分的依赖性进行了表征。最常观察到的反应是抑制性的，是由受体介导的内向整流钾电导激活所致。通常，该反应在应用激动剂后1 - 3秒内达到峰值，且未表现出脱敏现象。5-甲氧基-N，N-二甲基色胺在纹状体和海马体培养物中也产生了这种反应，并且对本研究中观察到的其他5-HT电流没有影响。选择性5-HT激动剂——8-羟基-2-（二正丙基氨基）四氢萘、1-（间氯苯基）哌嗪和1-（2-甲氧基苯基）哌嗪——并未激活这种外向电流反应。麦角新碱并未阻断5-HT激活的外向电流，且常常起激动剂的作用。在低串联电阻记录中这种反应消失了，低串联电阻记录有利于膜片电极与细胞之间的溶液交换。使用高电阻膜片电极可防止这种反应的消失，高电阻膜片电极会减缓这种交换。本研究中描述的另外2种反应是兴奋性的。它们比抑制性反应少见。其中一种兴奋性反应较快，达到峰值的时间约为200毫秒，持续时间为2 - 4秒。另一种较慢，达到峰值的时间为7 - 10秒，持续时间约为30 - 40秒。这两种反应都伴随着电导增加。快速兴奋性反应在去极化电位时反转，并以随电压变化的速率脱敏。甲氧氯普胺和d-筒箭毒碱完全且可逆地阻断了这种快速兴奋性反应，而麦角新碱则没有作用。在来自纹状体或海马体培养物的细胞进行细胞内透析期间，快速兴奋性反应并未消失。在来自这两个脑区的培养物中，缓慢兴奋性反应被麦角新碱阻断。即使在使用高电阻电极的膜片钳记录中，缓慢兴奋性反应也会消失。这种反应类似于对多巴胺、去甲肾上腺素和福斯高林的反应，已知所有这些物质都会在中枢神经系统中激活腺苷酸环化酶。
