acid sensing ion channel 1 in lateral hypothalamus contributes to breathing control酸敏感离子通道1在外侧下丘脑对呼吸的控制.pdfVIP

Acid Sensing Ion Channel 1 in Lateral Hypothalamus Contributes to Breathing Control 1 1 1 1 1 1 1 Nana Song , Guihong Zhang , Wenye Geng , Zibing Liu , Weizhong Jin , Li Li , Yinxiang Cao , 1 1,2 1 Danian Zhu , Jerry Yu , Linlin Shen * 1 Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China, 2 Department of Pulmonary Medicine, University of Louisville, Louisville, Kentucky, United States of America Abstract Acid-sensing ion channels (ASICs) are present in neurons and may contribute to chemoreception. Among six subunits of ASICs, ASIC1 is mainly expressed in the central nervous system. Recently, multiple sites in the brain including the lateral hypothalamus (LH) have been found to be sensitive to extracellular acidification. Since LH contains orexin neurons and innervates the medulla respiratory center, we hypothesize that ASIC1 is expressed on the orexin neuron and contributes to acid-induced increase in respiratory drive. To test this hypothesis, we used double immunofluorescence to determine whether ASIC1 is expressed on orexin neurons in the LH, and assessed integrated phrenic nerve discharge (iPND) in intact rats in response to acidification of the LH. We found that ASIC1 was co-localized with orexinA in the LH. Microinjection of acidified artificial cerebrospinal fluid increased the amplitude of iPND by 70% (pH 7.4 v.s. pH 6.5:1.0560.12 v.s. 1.7060.10, n = 6, P,0.001) and increased the respiratory drive (peak amplitude of iPND/inspiratory time, PA/Ti) by 40% (1.10 60.23 v.s. 1.5060.38, P,0.05). This stimulatory effect was abolished by blocking ASIC1 with a nonselective