Department of Pharmacology and Physiology, The George Washington University, 2300 Eye Street NW, Washington, DC 20037, USA.
Neuroscience. 2012 May 17;210:58-66. doi: 10.1016/j.neuroscience.2012.02.033. Epub 2012 Feb 24.
β-adrenergic receptors are a class of G protein-coupled receptors that have essential roles in regulating heart rate, blood pressure, and other cardiorespiratory functions. Although the role of β adrenergic receptors in the peripheral nervous system is well characterized, very little is known about their role in the central nervous system despite being localized in many brain regions involved in autonomic activity and regulation. Since parasympathetic activity to the heart is dominated by cardiac vagal neurons (CVNs) originating in the nucleus ambiguus (NA), β adrenergic receptors localized in the NA represent a potential target for modulating cardiac vagal activity and heart rate. This study tests the hypothesis that activation of β adrenergic receptors alters the membrane properties and synaptic neurotransmission to CVNs. CVNs were identified in brainstem slices, and membrane properties and synaptic events were recorded using the whole-cell voltage-clamp technique. The nonselective β agonist isoproterenol significantly decreased inhibitory GABAergic and glycinergic as well as excitatory glutamatergic neurotransmission to CVNs. In addition, the β(1)-selective receptor agonist dobutamine, but not β(2) or β(3) receptor agonists, significantly decreased inhibitory GABAergic and glycinergic and excitatory glutamatergic neurotransmission to CVNs. These decreases in neurotransmission to CVNs persisted in the presence of tetrodotoxin (TTX). These results provide a mechanism by which activation of adrenergic receptors in the brainstem can alter parasympathetic activity to the heart. Likely physiological roles for this adrenergic receptor activation are coordination of parasympathetic-sympathetic activity and β receptor-mediated increases in heart rate upon arousal.
β-肾上腺素受体是一类 G 蛋白偶联受体，在调节心率、血压和其他心肺功能方面起着重要作用。尽管β肾上腺素受体在外周神经系统中的作用已经得到很好的描述，但它们在中枢神经系统中的作用却知之甚少，尽管它们在许多参与自主活动和调节的脑区中都有定位。由于心脏的副交感神经活动主要由起源于疑核（NA）的心脏迷走神经元（CVN）支配，因此定位在 NA 中的β肾上腺素受体代表了调节心脏迷走神经活动和心率的潜在靶点。本研究检验了这样一个假设，即β肾上腺素受体的激活改变了 CVN 的膜特性和突触神经传递。在脑干切片中鉴定出 CVN，并使用全细胞膜片钳技术记录膜特性和突触事件。非选择性β激动剂异丙肾上腺素显著降低了 CVN 的抑制性 GABA 能和甘氨酸能以及兴奋性谷氨酸能神经传递。此外，β1-选择性受体激动剂多巴酚丁胺，而不是β2 或β3 受体激动剂，显著降低了 CVN 的抑制性 GABA 能和甘氨酸能以及兴奋性谷氨酸能神经传递。这些 CVN 神经传递的减少在存在河豚毒素（TTX）的情况下仍然存在。这些结果提供了一种机制，即脑干肾上腺素受体的激活可以改变心脏的副交感神经活动。这种肾上腺素受体激活的可能生理作用是协调副交感神经-交感神经活动以及β受体介导的觉醒时心率增加。
