Department of Internal Medicine and Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA.
Neuron. 2009 Dec 24;64(6):885-97. doi: 10.1016/j.neuron.2009.11.007.
Arterial baroreceptors provide a neural sensory input that reflexly regulates the autonomic drive of circulation. Our goal was to test the hypothesis that a member of the acid-sensing ion channel (ASIC) subfamily of the DEG/ENaC superfamily is an important determinant of the arterial baroreceptor reflex. We found that aortic baroreceptor neurons in the nodose ganglia and their terminals express ASIC2. Conscious ASIC2 null mice developed hypertension, had exaggerated sympathetic and depressed parasympathetic control of the circulation, and a decreased gain of the baroreflex, all indicative of an impaired baroreceptor reflex. Multiple measures of baroreceptor activity each suggest that mechanosensitivity is diminished in ASIC2 null mice. The results define ASIC2 as an important determinant of autonomic circulatory control and of baroreceptor sensitivity. The genetic disruption of ASIC2 recapitulates the pathological dysautonomia seen in heart failure and hypertension and defines a molecular defect that may be relevant to its development.
动脉压力感受器提供了一种神经感觉输入，反射性地调节循环的自主驱动。我们的目标是检验这样一个假设，即酸敏感离子通道（ASIC）家族的一个成员是 DEG/ENaC 超家族的重要决定因素，也是动脉压力感受器反射的重要决定因素。我们发现，结状神经节中的主动脉压力感受器神经元及其末梢表达 ASIC2。有知觉的 ASIC2 基因敲除小鼠发展为高血压，交感神经亢进和副交感神经对循环的抑制减弱，以及压力感受器反射的增益降低，所有这些都表明压力感受器反射受损。多种压力感受器活动的测量都表明，ASIC2 基因敲除小鼠的机械敏感性降低。研究结果将 ASIC2 定义为自主循环控制和压力感受器敏感性的重要决定因素。ASIC2 的遗传破坏再现了心力衰竭和高血压中所见的病理性自主神经功能障碍，并确定了一个分子缺陷，这可能与其发展有关。
