title: Acid-sensing ion channels are expressed in the ventrolateral medulla and contribute to central chemoreception.
abstract: The role of acid-sensing ion channels (ASICs) in the ventrolateral medulla (VLM) remains uncertain. Here, we found that ASIC1a and ASIC2 are widely expressed in rat medulla, and the expression level is higher at neonatal stage as compared to adult stage. The two ASIC subunits co-localized in medualla neurons. Furthermore, pH reduction triggered typical ASIC-type currents in the medulla, including the VLM. These currents showed a pH50value of 6.6 and were blocked by amiloride. Based on their sensitivity to psalmotoxin 1 (PcTx1) and zinc, homomeric ASIC1a and heteromeric ASIC1a/2 channels were likely responsible for acid-mediated currents in the mouse medulla. ASIC currents triggered by pH 5 disappeared in the VLM neurons from ASIC1-/-, but not ASIC2-/-mice. Activation of ASICs in the medulla also triggered neuronal excitation. Moreover, microinjection of artificial cerebrospinal fluid at a pH of 6.5 into the VLM increased integrated phrenic nerve discharge, inspiratory time and respiratory drive in rats. Both amiloride and PcTx1 inhibited the acid-induced stimulating effect on respiration. Collectively, our data suggest that ASICs are highly expressed in the medulla including the VLM, and activation of ASICs in the VLM contributes to central chemoreception.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.|Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Song
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Guan
authors.affiliation: Department of Basic Medical Science, School of Medicine, University of Missouri - Kansas City, Missouri 64108, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Basic Medical Science, School of Medicine, University of Missouri - Kansas City, Missouri 64108, USA.
authors.forename: Comron J
authors.initials: CJ
authors.lastname: Hassanzadeh
authors.affiliation: Department of Basic Medical Science, School of Medicine, University of Missouri - Kansas City, Missouri 64108, USA.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.|Division of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Qijun
authors.initials: Q
authors.lastname: Du
authors.affiliation: Department of Basic Medical Science, School of Medicine, University of Missouri - Kansas City, Missouri 64108, USA.|School of Mental Health, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, China.
authors.forename: Xiang-Ping
authors.initials: XP
authors.lastname: Chu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.|Shanghai Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention, Fudan University, Shanghai 200032, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Shen
mesh_terms: D062565:Acid Sensing Ion Channels / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D008526:Medulla Oblongata / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D051381:Rats
chemical_list: D062565:Acid Sensing Ion Channels