Angiotensin II regulates the activity of mouse suprachiasmatic nuclei neurons
Angiotensin II regulates the activity of mouse suprachiasmatic nuclei neurons
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DOI：
10.1016/j.neuroscience.2008.03.068
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发表时间：
2008-06-23
期刊：
影响因子：
3.3
通讯作者：
Piggins, H. D.
中科院分区：
文献类型：
--
作者：
Brown, T. M.;McLachlan, E.;Piggins, H. D.
神经肽信号在协调视交叉上核(SCN)内的细胞活动中起着关键作用，SCN是哺乳动物昼夜节律振荡器的主要位置。神经肽血管紧张素转换酶(AngII)及其同源受体AT(1)均由SCN细胞表达，但与其他SCN神经化学物质不同的是，对Angii在这个昼夜节律中的细胞作用知之甚少。我们采用多电极、多单位、细胞外电生理，结合全细胞电压和电流钳技术，研究了AngII在小鼠SCN切片上的作用。血管紧张素Ⅱ(0.001-10mU M)可剂量依赖性地刺激和抑制许多SCN神经元细胞外记录的神经元放电(接近60%)。AT(1)受体拮抗剂ZD7155(0.03 mU M)可阻断这两种作用，而GABA(A)受体拮抗剂荷包牡丹碱(20 MU M)可阻止抑制而不是激活。在(1)受体阻断剂本身抑制SCN神经元亚群(类似于30%)的放电，这种作用不被荷包牡丹碱阻断。在电压钳制的SCN神经元(-70 mV)上，AT(1)受体的激活呈剂量依赖性地增加动作电位驱动的GABAA受体介导的电流的频率，但不改变它们对外源性GABA的反应。在河豚毒素灌流的电流钳制的SCN神经元上，AngII诱导了膜去极化，并伴随着输入电阻的降低。结论：AT(1)受体被AngII激活，使SCN神经元去极化，刺激动作电位放电，导致小鼠SCN内GABA释放增加。此外，我们还首次提供了内源性AT(1)受体信号调节某些SCN神经元活动的证据。(C)2008年IBRO。爱思唯尔有限公司出版。保留所有权利。
Neuropeptide signaling plays key roles in coordinating cellular activity within the suprachiasmatic nuclei (SCN), site of the master circadian oscillator in mammals. The neuropeptide angiotensin If (ANGII) and its cognate receptor AT(1) are both expressed by SCN cells, but unlike other SCN neurochemicals, very little is known about the cellular actions of ANGII within this circadian clock.We used multi-electrode, multiunit, extracellular electrophysiology, coupled with whole-cell voltage and current clamp techniques to investigate the actions of ANGII in mouse SCN slices. ANGII (0.001-10 mu M) dose dependently stimulated and inhibited extracellularly recorded neuronal discharge in many SCN neurons (similar to 60%). Both actions were blocked by pre-treatment with the AT(1) receptor antagonist ZD7155 (0.03 mu M), while suppressions but not activations were prevented by pre-treatment with the GABA(A) receptor antagonist bicuculline (20 mu M). AT(1) receptor blockade itself suppressed discharge in a subset (similar to 30%) of SCN neurons, and this action was not blocked by bicuculline. In voltage-clamped SCN neurons (-70 mV), AT(1) receptor activation dose-dependently enhanced the frequency of action potential-driven, GABAA receptor-mediated currents, but did not alter their responses to exogenously applied GABA. In current-clamped SCN neurons perfused with tetrodotoxin, ANGII induced a membrane depolarization with a concomitant decrease in input resistance.In conclusion we show that AT(1) receptor activation by ANGII depolarizes SCN neurons and stimulates action potential firing, leading to increased GABA release in the mouse SCN. Additionally we provide the first evidence that endogenous AT(1) receptor signaling tonically regulates the activities of some SCN neurons. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.