Role of the Acid-Sensing Ion Channel 3 in Blood Volume Control

• Lee Cheng-Han

  Institute of Neuroscience, National Yang-Ming University Institute of Biomedical Sciences, Academia Sinica

• Sun Synthia H.

  Institute of Neuroscience, National Yang-Ming University

• Lin Shing-Hong

  Institute of Biomedical Sciences, Academia Sinica Graduate Institute of Life Sciences, National Defense Medical Center

• Chen Chih-Cheng

  Institute of Neuroscience, National Yang-Ming University Institute of Biomedical Sciences, Academia Sinica

抄録

Background: The mechanically sensitive volume receptors, primarily located in the venoatrial junction area, are essential for blood volume homeostasis. However, the molecular basis of the volume receptors is still unknown. Methods and Results: We hypothesized that the acid-sensing ion channel 3 (ASIC3) might be a candidate for the mechanically sensitive molecules expressed in the volume receptors. We examined the effect of Asic3 null mutation (Asic3^-/-) on blood volume expansion (BVE)-induced urine flow, neural activation, and atrial natriuretic peptide (ANP) release in mice. BVE-induced urine flow was lower in Asic3^-/- mice than in wild-type littermates. In addition, the stretch-activated channel blocker GdCl₃ further reduced the BVE-induced urine flow in Asic3^-/- mice. BVE increased phosphorylated extracellular signal-related kinase (pERK) immunoreactivity in nodose ganglia and many segments of dorsal root ganglia (DRG) in all mice, but pERK-positive neurons were fewer in Asic3^-/- mice or mice pretreated with GdCl₃ than in wild-type mice. Asic3 knockout selectively decreased BVE-induced pERK-immunoreactive neurons in nodose ganglia, and in C8 and T2 DRG. Moreover, BVE increased the circulating ANP level, which was abolished in Asic3^-/- mice and wild-type mice treated with GdCl₃. Asic3 knockout reduced the BVE-induced plasma ANP elevation in a GdCl₃-independent manner. Conclusions: ASIC3 is a molecular substrate involved in detecting the vessel stretch caused by BVE. (Circ J 2011; 75: 874-883)<br>

収録刊行物

• Circulation Journal

  Circulation Journal 75 (4), 874-883, 2011

  一般社団法人 日本循環器学会

キーワード

• ANP
• ASIC3
• Blood volume expansion
• Gadolinium
• pERK

詳細情報

• CRID: 1390282680078802304
• NII論文ID: 10028103227
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.cj-10-0607
• ISSN: 13474820
• ISSN: 13469843
• Web Site: http://www.jstage.jst.go.jp/article/circj/75/4/75_CJ-10-0607/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2011256754
• 本文言語コード: en
• データソース種別:
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  • Crossref
  • CiNii Articles
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