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

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.