Carter D A, Choong Y-T, Connelly A A, Bassi J K, Hunter N O, Thongsepee N, Llewellyn-Smith I J, Fong A Y, McDougall S J, Allen A M
Department of Physiology, The University of Melbourne, Melbourne, Victoria, Australia.
Cardiovascular Medicine and Human Physiology, School of Medicine, Flinders University, Bedford Park, South Australia, Australia; and.
Am J Physiol Regul Integr Comp Physiol. 2017 Oct 1;313(4):R438-R449. doi: 10.1152/ajpregu.00168.2017. Epub 2017 Jul 12.
Angiotensin II acts via two main receptors within the central nervous system, with the type 1A receptor (ATR) most widely expressed in adult neurons. Activation of the ATR in the nucleus of the solitary tract (NTS), the principal nucleus receiving central synapses of viscerosensory afferents, modulates cardiovascular reflexes. Expression of the ATR occurs in high density within the NTS of most mammals, including humans, but the fundamental electrophysiological and neurochemical characteristics of the ATR-expressing NTS neurons are not known. To address this, we have used a transgenic mouse, in which the ATR promoter drives expression of green fluorescent protein (GFP). Approximately one-third of ATR-expressing neurons express the catecholamine-synthetic enzyme tyrosine hydroxylase (TH), and a subpopulation of these stained for the transcription factor paired-like homeobox 2b (Phox2b). A third group, comprising approximately two-thirds of the ATR-expressing NTS neurons, showed Phox2b immunoreactivity alone. A fourth group in the ventral subnucleus expressed neither TH nor Phox2b. In whole cell recordings from slices in vitro, ATR-GFP neurons exhibited voltage-activated potassium currents, including the transient outward current and the M-type potassium current. In two different mouse strains, both ATR-GFP neurons and TH-GFP neurons showed similar ATR-mediated depolarizing responses to superfusion with angiotensin II. These data provide a comprehensive description of ATR-expressing neurons in the NTS and increase our understanding of the complex actions of this neuropeptide in the modulation of viscerosensory processing.
血管紧张素II通过中枢神经系统内的两种主要受体发挥作用，其中1A型受体（ATR）在成年神经元中表达最为广泛。孤束核（NTS）是接受内脏感觉传入神经中枢突触的主要核团，激活该核团中的ATR可调节心血管反射。大多数哺乳动物（包括人类）的NTS中ATR表达密度很高，但表达ATR的NTS神经元的基本电生理和神经化学特征尚不清楚。为了解决这个问题，我们使用了一种转基因小鼠，其中ATR启动子驱动绿色荧光蛋白（GFP）的表达。大约三分之一表达ATR的神经元表达儿茶酚胺合成酶酪氨酸羟化酶（TH），其中一小部分细胞转录因子配对样同源框2b（Phox2b）染色阳性。第三组，约占表达ATR的NTS神经元的三分之二，仅显示Phox2b免疫反应性。腹侧亚核中的第四组既不表达TH也不表达Phox2b。在体外切片的全细胞记录中，ATR-GFP神经元表现出电压激活的钾电流，包括瞬时外向电流和M型钾电流。在两种不同的小鼠品系中，ATR-GFP神经元和TH-GFP神经元对血管紧张素II的灌注均表现出相似的ATR介导的去极化反应。这些数据全面描述了NTS中表达ATR的神经元，并增进了我们对这种神经肽在调节内脏感觉处理中复杂作用的理解。
