Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND58203, USA.
J Physiol. 2021 Jun;599(12):3101-3119. doi: 10.1113/JP281260. Epub 2021 Apr 27.
Activation of V vasopressin receptors facilitates neuronal excitability in the medial nucleus of central amygdala (CeM) V receptor activation excites about 80% CeM neurons by opening a cationic conductance and about 20% CeM neurons by suppressing an inwardly rectifying K (Kir) channel The cationic conductance activated by V receptors is identified as TRPC5 channels PLCβ-mediated depletion of PIP is involved in V receptor-elicited excitation of CeM neurons Intracellular Ca release and PKC are unnecessary for V receptor-mediated excitation of CeM neurons ABSTRACT: Arginine vasopressin (AVP) serves as a hormone in the periphery to modulate water homeostasis and a neuromodulator in the brain to regulate a diverse range of functions including anxiety, social behaviour, cognitive activities and nociception. The amygdala is an essential brain region involved in modulating defensive and appetitive behaviours, pain and alcohol use disorders. Whereas activation of V receptors in the medial nucleus of the central amygdala (CeM) increases neuronal excitability, the involved ionic and signalling mechanisms have not been determined. We found that activation of V receptors in the CeM facilitated neuronal excitability predominantly by opening TRPC5 channels, although AVP excited about one fifth of the CeM neurons via suppressing an inwardly rectifying K (Kir) channel. G proteins and phospholipase Cβ (PLCβ) were required for AVP-elicited excitation of CeM neurons, whereas intracellular Ca release and the activity of protein kinase C were unnecessary. Prevention of the depletion of phosphatidylinositol 4,5-bisphosphate (PIP ) blocked AVP-induced excitation of CeM neurons, suggesting that PLCβ-mediated depletion of PIP is involved in AVP-mediated excitation of CeM neurons. Our results may provide a cellular and molecular mechanism to explain the anxiogenic effects of AVP in the amygdala.
血管升压素 V 受体的激活促进了中杏仁核（CeM）神经元的兴奋性血管升压素 V 受体的激活通过打开阳离子电导，使大约 80%的 CeM 神经元兴奋，通过抑制内向整流钾（Kir）通道，使大约 20%的 CeM 神经元兴奋血管升压素 V 受体激活的阳离子电导被鉴定为 TRPC5 通道 PLCβ介导的 PIP 的耗竭参与了血管升压素 V 受体诱导的 CeM 神经元兴奋细胞内 Ca 释放和 PKC 对于血管升压素 V 受体介导的 CeM 神经元兴奋不是必需的摘要：精氨酸血管升压素（AVP）作为外周激素，调节水稳态；作为脑内神经调质，调节多种功能，包括焦虑、社会行为、认知活动和痛觉。杏仁核是调节防御和摄食行为、疼痛和酒精使用障碍的重要脑区。虽然中杏仁核（CeM）内血管升压素 V 受体的激活增加了神经元的兴奋性，但涉及的离子和信号机制尚未确定。我们发现，CeM 内血管升压素 V 受体的激活主要通过打开 TRPC5 通道促进神经元兴奋性，尽管 AVP 通过抑制内向整流钾（Kir）通道兴奋大约五分之一的 CeM 神经元。G 蛋白和磷脂酶 Cβ（PLCβ）是 AVP 诱导的 CeM 神经元兴奋所必需的，而细胞内 Ca 释放和蛋白激酶 C 的活性是不必要的。抑制磷脂酰肌醇 4,5-二磷酸（PIP）的耗竭阻断了 AVP 诱导的 CeM 神经元兴奋，提示 PLCβ 介导的 PIP 耗竭参与了 AVP 介导的 CeM 神经元兴奋。我们的结果可能为解释杏仁核内 AVP 的焦虑作用提供了一个细胞和分子机制。
