Williams Sandile E J, Wootton Phillippa, Mason Helen S, Bould Jonathan, Iles David E, Riccardi Daniela, Peers Chris, Kemp Paul J
School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK.
Science. 2004 Dec 17;306(5704):2093-7. doi: 10.1126/science.1105010. Epub 2004 Nov 4.
Modulation of calcium-sensitive potassium (BK) channels by oxygen is important in several mammalian tissues, and in the carotid body it is crucial to respiratory control. However, the identity of the oxygen sensor remains unknown. We demonstrate that hemoxygenase-2 (HO-2) is part of the BK channel complex and enhances channel activity in normoxia. Knockdown of HO-2 expression reduced channel activity, and carbon monoxide, a product of HO-2 activity, rescued this loss of function. Inhibition of BK channels by hypoxia was dependent on HO-2 expression and was augmented by HO-2 stimulation. Furthermore, carotid body cells demonstrated HO-2-dependent hypoxic BK channel inhibition, which indicates that HO-2 is an oxygen sensor that controls channel activity during oxygen deprivation.
氧对钙敏感性钾（BK）通道的调节在多种哺乳动物组织中具有重要意义，在颈动脉体中，这对呼吸控制至关重要。然而，氧传感器的身份仍然未知。我们证明，血红素加氧酶-2（HO-2）是BK通道复合物的一部分，并在常氧条件下增强通道活性。敲低HO-2表达会降低通道活性，而HO-2活性产物一氧化碳可挽救这种功能丧失。缺氧对BK通道的抑制作用依赖于HO-2表达，并因HO-2刺激而增强。此外，颈动脉体细胞表现出HO-2依赖性的缺氧BK通道抑制，这表明HO-2是一种在缺氧期间控制通道活性的氧传感器。
