Ionic mechanism of the slow afterdepolarization induced by muscarinic receptor activation in rat prefrontal cortex
Ionic mechanism of the slow afterdepolarization induced by muscarinic receptor activation in rat prefrontal cortex
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DOI：
10.1152/jn.1998.80.3.1197
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发表时间：
1998-09-01
影响因子：
2.5
通讯作者：
Andrade, R
中科院分区：
文献类型：
--
作者：
Haj-Dahmane, S;Andrade, R
哺乳动物的前额皮质接受来自皮质下区域的密集的胆碱能神经支配。我们以前已经表明，胆碱能刺激大鼠前额叶皮层的第V层锥体神经元的结果在去极化和缓慢后去极化（sADP）的外观。在目前的报告中，我们研究了潜在的sADP的机制与使用锋利的微电极和全细胞记录技术在体外脑切片。乙酰胆碱（ACh）和卡巴胆碱诱导前额叶皮层第V层锥体细胞出现sADP的能力被阿托品以可克服的方式拮抗，并被毒蕈碱或oxotremorine的应用所模仿。这些结果表明，ACh作用于毒蕈碱受体，诱导sADP。在许多细胞类型中，后电位是由钙离子流入细胞而触发的。因此，我们研究了钙内流可能是sADP产生的触发因素的可能性。与这种可能性相一致，缓冲细胞内钙减少或取消sADP，但对直接毒蕈碱受体诱导的去极化也在这些细胞中看到的影响不大。这些结果与先前观察到的钙通道阻滞剂抑制sADP相结合，表明sADP是由继发于钙流入细胞的细胞内钙升高引起的。使用离子取代实验检查了sADP（I-sADP）电流的离子基础。用N-甲基-D-葡糖胺（NMDG）替代细胞外钠，发现I-sADP的幅度以分级的方式降低。与此相反，没有发现钾通道或氯通道参与sADP或I-sADP的产生的明确证据，这一结果表明I-sADP是由流入细胞的钠艾奥纳携带的。然而，I-sADP对细胞外钠的依赖性比纯钠电流预期的要小。我们解释这些结果表明，sADP是最有可能介导的非选择性阳离子通道。在不同电压下检查sADP的电流表明，该电流也是电压依赖性的，随着超极化而关闭。我们的结论是，在大鼠皮层毒蕈碱受体激活引起的sADP介导的主要是由钙和电压敏感的非选择性阳离子电流。该电流可能是ACh调节前额叶皮层神经元兴奋性的重要机制。
The mammalian prefrontal cortex receives a dense cholinergic innervation from subcortical regions. We previously have shown that cholinergic stimulation of layer V pyramidal neurons of the rat prefrontal cortex results in a depolarizaton and the appearance of a slow afterdepolarization (sADP). In the current report we examine the mechanism underlying the sADP with the use of sharp microelectrode and whole cell recording techniques in in vitro brain slices. The ability of acetylcholine (ACh) and carbachol to induce the appearance of an sADP in pyramidal cells of layer V of prefrontal cortex is antagonized in a surmountable manner by atropine and is mimicked by application of muscarine or oxotremorine. These results indicate that ACh acts on muscarinic receptors to induce the sADP. In many cell types afterpotentials are triggered by calcium influx into the cell. Therefore we examined the possibility that calcium influx might be the trigger for the generation of the sADP. Consistent with this possibility, buffering intracellular calcium reduced or abolished the sADP but had little effect on the direct muscarinic receptor-induced depolarization also seen in these cells. These results, coupled to the previous observation that calcium channel blockers inhibit the sADP, indicated that the sADP results from a rise in intracellular calcium secondary to calcium influx into the cell. The ionic basis for the current underlying the sADP (I-sADP) was examined with the use of ion substitution experiments. The amplitude of I-sADP was found to be reduced in a graded fashion by replacement of extracellular sodium with N-methyl-D-glucamine (NMDG). In contrast no clear evidence for the involvement of potassium or chloride channels in the: generation of the sADP or I-sADP could be found. This result indicated that I-sADP is carried by sodium iona flowing into the cell. However, the dependence of I-sADP on extracellular sodium was less pronounced than expected for a pure sodium current. We interpret these results to indicate that the sADP is most likely mediated by nonselective cation channels. Examination of the current underlying the sADP at different voltages indicated that this current was also voltage dependent, turning off with hyperpolarization. We conclude that the sADP elicited by muscarinic receptor activation in rat cortex is mediated predominantly by a calcium- and voltage-sensitive nonselective cation current. This current could represent an important mechanism through which ACh can regulate neuronal excitability in prefrontal cortex.