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

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概要

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• 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)

• 2011-03-25

著者

• Lee Cheng-han

  Institute Of Neuroscience National Yang-ming University

• Chen Chih-cheng

  Institute Of Neuroscience National Yang-ming University

• Chen Chih-cheng

  Institute Of Biomedical Sciences Academia Sinica

• SUN Synthia

  Institute of Neuroscience, National Yang-Ming University

• LIN Shing-Hong

  Institute of Biomedical Sciences, Academia Sinica

• Lin Shing-hong

  Institute Of Biomedical Sciences Academia Sinica

• Sun Synthia

  Institute Of Neuroscience National Yang-ming University

関連論文

• PE-036 Abnormal cardiac autonomic regulation and susceptibility to cardiac ischemia in mice lack of ASIC3(Autonomic nervous system(03)(H),Poster Session(English),The 72nd Annual Scientific Meeting of the Japanese Circulation Society)
• Acid-Sensing Ion Channel 3, But Not Capsaicin Receptor TRPV1, Plays a Protective Role in Isoproterenol-Induced Myocardial Ischemia in Mice
• Role of the Acid-Sensing Ion Channel 3 in Blood Volume Control

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