5-HYDROXYTRYPTAMINE2 AND 5-HYDROXYTRYPTAMINE1A RECEPTORS MEDIATE OPPOSING RESPONSES ON MEMBRANE EXCITABILITY IN RAT-ASSOCIATION CORTEX
5-HYDROXYTRYPTAMINE2 AND 5-HYDROXYTRYPTAMINE1A RECEPTORS MEDIATE OPPOSING RESPONSES ON MEMBRANE EXCITABILITY IN RAT-ASSOCIATION CORTEX
复制标题
DOI：
10.1016/0306-4522(91)90128-b
复制
发表时间：
1991-01-01
期刊：
影响因子：
3.3
通讯作者：
ANDRADE, R
中科院分区：
文献类型：
--
作者：
ARANEDA, R;ANDRADE, R
在离体大鼠脑片上，用细胞内记录技术观察了5-羟色胺对内侧前额叶皮质V层锥体细胞的影响。 5-羟色胺（0.3-100 μ M）浴给药产生两种不同的反应，可区分为生理和免疫反应。 这些反应中的第一个是膜超极化。 5-羟色胺的这种作用与输入电阻的降低有关，并且独立于跨膜氯离子梯度，这表明它是由钾电导的增加介导的。 5-羟色胺诱导超极化的能力被（+/-）-8-羟基-二丙基氨基四氢萘氢溴酸盐模拟，并被BMY 7378和螺哌隆阻断，但不被酮色林阻断，表明它是由5-羟色胺1A亚型受体的激活介导的。这些细胞中尖峰脉冲爆发后的后超极化被缓慢去极化后电位取代，并且尖峰频率调节降低。 这些作用被4-溴-2，5-二甲氧基苯基异丙胺模拟，并被酮色林和低浓度的螺哌隆拮抗，表明它们是由5-羟色胺2受体的激活介导的。 有趣的是，通过激活毒蕈碱和α-1-肾上腺素能受体可以在这些细胞中引起定性相同的反应，这表明5-羟色胺2、毒蕈碱和α-1-肾上腺素能受体会聚到一组共同的膜机制上以增加细胞的兴奋性。大多数锥体神经元似乎在其膜表面上表达两种受体亚型。 两种受体亚型的共激活导致对强兴奋性刺激的反应性的选择性增强，对较弱刺激的影响不大。 两种5-羟色胺受体在同一细胞中介导对膜兴奋性的相反作用，这一矛盾的存在提供了一种灵活的机制，5-羟色胺可能通过这种机制调节锥体神经元如何将传入的兴奋性刺激编码到放电活动中。
The effects of serotonin on pyramidal cells of layer V of the medial prefrontal cortex were examined using intracellular recording techniques in rat brain slices in vitro. Bath administration of serotonin (0.3-100-mu-M) produced two distinct responses which could be differentiated physiologically and pharmacologically. The first of these responses was a membrane hyperpolarization. This effect of serotonin was associated with a decrease in input resistance and was independent of the transmembrane chloride gradient, suggesting that it was mediated by an increase in potassium conductance. The ability of serotonin to induce a hyperpolarization was mimicked by (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide and was blocked by BMY 7378 and spiperone but not by ketanserin, indicating that it was mediated by the activation of receptors of the 5-hydroxytryptamine1A subtype.The second response to serotonin involved a membrane depolarization, the replacement of the afterhyperpolarization that follows a burst of spikes in these cells by a slow depolarizing afterpotential, and a decrease in spike frequency accommodation. These effects were mimicked by 4-bromo-2,5-dimethoxyphenyl-isopropylamine and antagonized by ketanserin and by low concentrations of spiperone, indicating that they were mediated by the activation of 5-hydroxytryptamine2 receptors. Interestingly, qualitatively identical responses could be elicited in these cells by activation of muscarinic and alpha-1-adrenergic receptors suggesting that 5-hydroxytryptamine2, muscarinic and alpha-1-adrenergic receptors converge onto a common set of membrane mechanisms to increase cellular excitability.Although 5-hydroxytryptamine1A and 5-hydroxytryptamine2 receptors mediated opposing effects on membrane excitability, most pyramidal neurons appeared to express both receptor subtypes on their membrane surface. The coactivation of both receptor subtypes resulted in a selective enhancement of responsiveness to strong excitatory stimuli with little effect on weaker stimuli. The paradoxical presence of two serotonin receptors mediating opposite effects on membrane excitability in the same cell provides a flexible mechanism by which serotonin might regulate how pyramidal neurons encode incoming excitatory stimuli onto firing activity.