Persistent Cytosolic Ca 2+ Increase Induced by Angiotensin II at Nanomolar Concentrations in Acutely Dissociated Subfornical Organ (SFO) Neurons of Rats
Persistent Cytosolic Ca 2+ Increase Induced by Angiotensin II at Nanomolar Concentrations in Acutely Dissociated Subfornical Organ (SFO) Neurons of Rats
复制标题
纳摩尔浓度血管紧张素 II 在大鼠急性分离穹窿下器官 (SFO) 神经元中诱导胞浆 Ca 2 持续增加
DOI：
10.1016/j.brainres.2019.05.014
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发表时间：
2019
期刊：
影响因子：
2.9
通讯作者：
Izumi Shibuya
中科院分区：
文献类型：
--
作者：
Yu Izumisawa;Keiko Tanaka-Yamamoto;John Ciriello;Naoki Kitamura;Izumi Shibuya
血管紧张素II（angiotensin II，AII）是通过穹窿下器官（subfornicalorgan，SFO）感受到的，从而引起饮酒行为和自主神经功能的改变。皮摩尔浓度的AII已被证明可诱导SFO神经元中的Ca 2+振荡并增加自发Ca 2+振荡的幅度和频率。本研究采用Fura-2钙离子成像技术在急性分离的SFO神经元中研究纳摩尔浓度的AII的影响。在纳摩尔浓度下，AII诱导初始[Ca 2 +] i峰，随后持续[Ca 2 +] i增加，持续时间超过1小时。相比之下，[Ca 2 +] i对50 mM K+、最大有效浓度的谷氨酸、卡巴胆碱和加压素以及皮摩尔浓度的AII的反应在20分钟内恢复到基础水平。AII引起的[Ca ~（2+）] i升高可被AT_1拮抗剂氯沙坦阻断。然而，当在持续阶段加入氯沙坦时，没有效果。细胞外Ca ~（2+）清除可抑制持续相，L和P/Q型Ca ~（2+）通道阻断剂可显著抑制持续相，但抑制Ca ~（2+）库Ca ~（2+）ATP酶对持续相无影响。持续相被GABA可逆地抑制，并被CaMK和PKC抑制剂抑制。这些结果表明，纳摩尔浓度的AII引起的持续性[Ca ~（2+）] i增加是由AT_1受体激活引起的，并通过L和P/Q型Ca ~（2+）通道的Ca ~（2+）内流机制维持，CaMK和PKC参与了这一过程。AII在高病理生理水平引起的持续性[Ca ~（2+）] i升高可能在改变SFO神经元功能中起重要作用。
It is known that angiotensin II (AII) is sensed by subfornical organ (SFO) to induce drinking behaviors and autonomic changes. AII at picomolar concentrations have been shown to induce Ca2+oscillations and increase in the amplitude and frequency of spontaneous Ca2+oscillations in SFO neurons. The present study was conducted to examine effects of nanomolar concentrations of AII using the Fura-2 Ca2+-imaging technique in acutely dissociated SFO neurons. AII at nanomolar concentrations induced an initial [Ca2+]ipeak followed by a persistent [Ca2+]iincrease lasting for longer than 1 hour. By contrast, [Ca2+]iresponses to 50 mM K+, maximally effective concentrations of glutamate, carbachol, and vasopressin, and AII given at picomolar concentrations returned to the basal level within 20 min. The AII-induced [Ca2+]iincrease was blocked by the AT1 antagonist losartan. However, losartan had no effect when added during the persistent phase. The persistent phase was suppressed by extracellular Ca2+ removal, significantly inhibited by blockers of L and P/Q type Ca2+channels , but unaffected by inhibition of Ca2+store Ca2+ATPase. The persistent phase was reversibly suppressed by GABA and inhibited by CaMK and PKC inhibitors. These results suggest that the persistent [Ca2+]iincrease evoked by nanomolar concentrations of AII is initiated by AT1 receptor activation and maintained by Ca2+entry mechanisms in part through L and P/Q type Ca2+channels, and that CaMK and PKC are involved in this process. The persistent [Ca2+]iincrease induced by AII at high pathophysiological levels may have a significant role in altering SFO neuronal functions.