Journal of Capital Medical University ›› 2013, Vol. 34 ›› Issue (2): 224-231.doi: 10.3969/j.issn.1006-7795.2013.02.013

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Sildenafil inhibits hypoxia-induced voltage-dependent potassium channels downregulation in human pulmonary artery smooth muscle cells

MAO Ting1,2, WANG Yuexiu1,2, LIU Jie1,2, LI Jing1,2, WANG Jun1,2   

  1. 1. Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China;
    2. Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
  • Received:2012-10-24 Online:2013-04-21 Published:2013-04-17
  • Supported by:

    This study was supported by the 973 program(2009CB522107), National Natural Science Foundation of China(81070042), Major International Collaborative Research Foundation of China(30810103904), Overseas and Hong Kong and Macao Scholars of Collaborative Research Foundation of China(81228001), Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders in Capital Medical University(RPCD201201, 2011HXFB04), Basis-clinical Research Co-operation Fund of Capital Medical University(12JL15), The Fundation of Scientific Research Common Program of Beijing Municipal Commission of Education(KM201310025004), Natural Science Foundation of Lingxia(NZ1220).

Abstract:

Objective To investigate the effect of sildenafil on hypoxia-induced voltage-dependent potassium channels(Kv) downregulation in human pulmonary artery smooth muscle cells(PASMCs). Methods Patch clamp techniques were applied to record K+ currents from human PASMCs cultured with SMBM(2% FBS) in normoxia or hypoxia(3% O2) in the absence or presence of sildenafil(100 nM) for 72 h. Furthermore, the effect of sildenafil on the Kv channel subfamily was examined via the special anti-Kv1.5 antibody dialysis. Real-time PCR and Western blotting techniques were performed to detect the gene transcription and protein expression of Kv1.5 channel in human PASMCs. Results Hypoxia obviously inhibited whole-cell K+ currents in PASMCs; sildenafil significantly restored hypoxia-decreased K+ currents; Kv1.5 channel is the target of the modulation of sildenafil on Kv in hypoxic PASMCs; sildenafil partially restored hypoxia-inhibited mRNA and protein expression of Kv1.5 channel in PASMCs. Conclusion Sildenafil inhibits hypoxia-induced voltage-dependent potassium channels downregulation in human PASMCs.

Key words: sildenafil, voltage-dependent potassium channels, human pulmonary artery smooth muscle cells

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