Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Xi'an Jiaotong University College of Stomatology, 98# Xiwu Road, Xi'an, Shaanxi, 710004, PR China; Department of Prosthodontics, Xi'an Jiaotong University College of Stomatology, 98# Xiwu Road, Xi'an, Shaanxi, 710004, PR China.
Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Science, 76# W. Yanta Road, Xi'an, Shaanxi, 710061, PR China.
Neuropharmacology. 2018 May 1;133:334-344. doi: 10.1016/j.neuropharm.2018.02.009. Epub 2018 Feb 12.
The central nucleus of the amygdala (CeA) is critical in the regulation of sodium appetite. Angiotensin II (Ang II) is important in the generation of sodium appetite and may function as a neurotransmitter or modulator to affect the synaptic transmission and the excitability of neurons. However, the role of Ang II in the CeA remains unclear. In this study, we determined the effects of Ang II on the excitatory and inhibitory synaptic inputs to the CeA neurons in brain slices with whole-cell patch-clamp recordings. Ang II (0.5-5 μM) significantly potentiated the amplitude of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) in a concentration-dependent manner. Ang II (2 μM) significantly increased the amplitude of miniature GABAergic inhibitory postsynaptic currents (mIPSCs) without affecting the frequency. This effect was blocked by Ang II type 1 (AT) receptor antagonist, losartan. One mM guanosine 5'-O-(-2-thiodiphosphate) (GDP-β-s) in the pipette internal solution eliminated the facilitatory effect of Ang II on GABAergic synaptic transmission. In contrast, Ang II had no effect on the spontaneous glutamatergic excitatory postsynaptic currents (EPSCs) and did not alter the frequency and amplitude of miniature EPSCs at concentrations that facilitated IPSCs. Furthermore, Ang II decreased the firing activity of CeA neurons, and this effect was abolished by losartan and GDP-β-s. In addition, Ang II failed to inhibit CeA neurons in the presence of bicuculline. These data provide substantial new evidence that Ang II inhibits the CeA neurons by facilitation of GABAergic synaptic input efficacy through activation of postsynaptic AT receptors.
杏仁中央核（CeA）在调节钠食欲中起关键作用。血管紧张素 II（Ang II）在产生钠食欲中很重要，它可能作为神经递质或调节剂发挥作用，影响突触传递和神经元的兴奋性。然而，Ang II 在 CeA 中的作用尚不清楚。在这项研究中，我们通过全细胞膜片钳记录确定了 Ang II 对脑切片中 CeA 神经元兴奋性和抑制性突触输入的影响。Ang II（0.5-5 μM）以浓度依赖性方式显著增强自发性 GABA 能抑制性突触后电流（IPSCs）的幅度。Ang II（2 μM）显著增加微小 GABA 能抑制性突触后电流（mIPSCs）的幅度，而不影响频率。这种作用被 Ang II 型 1（AT）受体拮抗剂洛沙坦阻断。在管内液中加入 1 mM 鸟嘌呤 5'-O-（-2-硫代二磷酸盐）（GDP-β-s）消除了 Ang II 对 GABA 能突触传递的促进作用。相比之下，Ang II 对自发性谷氨酸能兴奋性突触后电流（EPSCs）没有影响，并且在促进 IPSCs 的浓度下，不改变微小 EPSCs 的频率和幅度。此外，Ang II 降低了 CeA 神经元的放电活性，而这种作用被洛沙坦和 GDP-β-s 消除。此外，在存在荷包牡丹碱的情况下，Ang II 未能抑制 CeA 神经元。这些数据提供了大量新的证据，表明 Ang II 通过激活突触后 AT 受体促进 GABA 能突触输入效率来抑制 CeA 神经元。
