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Large-conductance Ca2+-activated K+ currents blocked and impaired by homocysteine in human and rat mesenteric artery smooth muscle cells

机译:同型半胱氨酸在人和大鼠肠系膜动脉平滑肌细胞中阻断和削弱大传导性Ca2 +激活的K +电流

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Plenty of evidence suggests that increased blood levels of homocysteine (Hcy) are an independent risk factor for the development of vascular diseases, but the underlying mechanisms are not well understood. It is well known that the larger conductance Ca2+-activated K+ channels (BKCa) play an essential role in vascular function, so the present study was conducted to determine direct effects of Hcy on BKCa channel properties of smooth muscle cells. Whole-cell patch–clamp recordings were made in mesenteric artery smooth muscle cells isolated from normal rat and patients to investigate effects of 5, 50 and 500 μM Hcy on BKCa, the main current mediating vascular responses in these cells. In human artery smooth muscle cells, maximum BKCa density (measured at + 60 mV) was inhibited by about 24% (n = 6, P < 0.05). In rat artery smooth muscle cells, maximum BKCa density was decreased by approximately 27% in the presence of 50 μM Hcy (n = 8, P < 0.05). In addition, when rat artery smooth muscle cells was treated with 50 μM Hcy for 24 h, maximum BKCa density decreased by 58% (n = 5, P < 0.05). These data suggest that Hcy significantly inhibited BKCa currents in isolated human and rat artery smooth muscle cells. BKCa reduced and impaired by elevated Hcy levels might contribute to abnormal vascular diseases.
机译:大量证据表明,高半胱氨酸(Hcy)的血药水平升高是血管疾病发展的独立危险因素,但其潜在机制尚不清楚。众所周知,较大的电导Ca2 +激活的K +通道(BKCa)在血管功能中起着至关重要的作用,因此,本研究旨在确定Hcy对平滑肌细胞BKCa通道特性的直接影响。在分离自正常大鼠和患者的肠系膜动脉平滑肌细胞中进行全细胞膜片钳记录,以研究5、50和500μMHcy对BKCa的影响,BKCa是介导这些细胞中血管反应的主要电流。在人动脉平滑肌细胞中,最大BKCa密度(在+ 60 mV处测量)被抑制约24%(n = 6,P <0.05)。在大鼠动脉平滑肌细胞中,在50μMHcy存在下,最大BKCa密度降低了约27%(n = 8,P <0.05)。此外,用50μMHcy处理大鼠动脉平滑肌细胞24小时后,最大BKCa密度降低了58%(n = 5,P <0.05)。这些数据表明,Hcy可显着抑制人和大鼠动脉平滑肌细胞中的BKCa电流。 Hcy水平升高会降低和削弱BKCa,可能导致异常血管疾病。

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