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钙调蛋白在背缝核中的调节作用在戊巴比妥诱导的非快速眼动睡眠和快速眼动睡眠调节中起着重要作用。

Ca²+ modulation in dorsal raphe plays an important role in NREM and REM sleep regulation during pentobarbital hypnosis.

机构信息

Department of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing 100191, China.

出版信息

Brain Res. 2011 Jul 27;1403:12-8. doi: 10.1016/j.brainres.2011.05.064. Epub 2011 Jun 6.

Abstract

Our previous studies indicated that L-type calcium channel blocker diltiazem could potentiate pentobarbital-induced hypnosis through serotonergic system. In view of the important role of dorsal raphe nucleus (DRN) on the sleep regulation and the pharmacological actions of calcium channel blocker, we presumed that Ca(2+) in the DRN may play an important role in sleep regulation in pentobarbital treated rats. Therefore, we investigated whether the Ca(2+) modulation in DRN by the microinjection of L-type Ca(2+) channel antagonist diltiazem, agonist BAY-K-8644, Ca(2+) chelator EGTA and CaCl(2) would alter the sleep parameters in pentobarbital treated rats. Results showed that perfusion of the agents attenuating Ca(2+) function, such as diltiazem (5 or 20 nmol) or EGTA (3 or 6 pmol) into DRN significantly increased pentobarbital (35 mg/kg, i.p.)-induced total sleep (TS), non-rapid eye movement (NREM) sleep and the slow wave sleep (SWS) ratio in NREM sleep. On the contrary, the DRN injection of the agents improving Ca(2+) function, such as BAY-K-8644 (10 nmol) or CaCl(2) (50 or 100 nmol) significantly reduced pentobarbital (35 mg/kg, i.p.)-induced TS, NREM sleep, rapid eye movement (REM) sleep and REM sleep ratio in TS without influence on SWS. These results suggested that the suppression of Ca(2+) function in DRN could increase NREM sleep including SWS, and the elevation of Ca(2+) function could reduce both NREM and REM sleep in pentobarbital treated rats.

摘要

我们之前的研究表明,L 型钙通道阻滞剂地尔硫卓可以通过 5-羟色胺能系统增强戊巴比妥诱导的催眠作用。鉴于背缝核(DRN)在睡眠调节和钙通道阻滞剂药理学作用中的重要作用,我们推测 DRN 中的 Ca2+可能在戊巴比妥处理的大鼠睡眠调节中发挥重要作用。因此,我们研究了通过向 DRN 内微注射 L 型钙通道拮抗剂地尔硫卓、激动剂 BAY-K-8644、Ca2+螯合剂 EGTA 和 CaCl2 来调节 Ca2+是否会改变戊巴比妥处理的大鼠的睡眠参数。结果表明,灌流 Ca2+功能减弱剂,如地尔硫卓(5 或 20nmol)或 EGTA(3 或 6pmol),可显著增加戊巴比妥(35mg/kg,ip)诱导的总睡眠时间(TS)、非快速眼动(NREM)睡眠和 NREM 睡眠中的慢波睡眠(SWS)比例。相反,向 DRN 内注射 Ca2+功能增强剂,如 BAY-K-8644(10nmol)或 CaCl2(50 或 100nmol),可显著减少戊巴比妥(35mg/kg,ip)诱导的 TS、NREM 睡眠、快速眼动(REM)睡眠和 TS 中的 REM 睡眠比例,而对 SWS 没有影响。这些结果表明,DRN 中 Ca2+功能的抑制可增加 NREM 睡眠,包括 SWS,而 Ca2+功能的升高可减少戊巴比妥处理的大鼠的 NREM 和 REM 睡眠。

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