Huazhong University of Science and Technology, Wuhan, PR China.
Free Radic Res. 2010 Sep;44(9):1004-12. doi: 10.3109/10715762.2010.495126.
The inhibitory or activating effect of H(2)O(2) on large conductance calcium and voltage-dependent potassium (BK(Ca)) channels has been reported. However, the mechanism by which this occurs is unclear. In this paper, BK(Ca) channels encoded by mouse Slo were expressed in HEK 293 cells and BK(Ca) channel activity was measured by electrophysiology. The results showed that H(2)O(2) inhibited BK(Ca) channel activity in inside-out patches but enhanced BK(Ca) channel activity in cell-attached patches. The inhibition by H(2)O(2) in inside-out patches may be due to oxidative modification of cysteine residues in BK(Ca) channels or other membrane proteins that regulate BK(Ca) channel function. PI3K/AKT signaling modulates the H(2)O(2)-induced BK(Ca) channel activation in cell-attached patches. BK(Ca) channels and PI3K signaling pathway were involved in H(2)O(2)-induced vasodilation and H(2)O(2)-induced vasodilation by PI3K pathway was mainly due to modulation of BK(Ca) channel activity.
已有报道称，H(2)O(2) 对大电导钙和电压依赖性钾 (BK(Ca)) 通道具有抑制或激活作用。然而，其发生的机制尚不清楚。本文通过在 HEK 293 细胞中表达由小鼠 Slo 编码的 BK(Ca) 通道，并用电生理学方法测量 BK(Ca) 通道活性，结果表明 H(2)O(2) 抑制了胞内片上 BK(Ca) 通道的活性，但增强了细胞贴附片上 BK(Ca) 通道的活性。H(2)O(2) 在胞内片中的抑制作用可能是由于 BK(Ca) 通道或其他调节 BK(Ca) 通道功能的膜蛋白中半胱氨酸残基的氧化修饰所致。PI3K/AKT 信号通路调节细胞贴附片中 H(2)O(2)诱导的 BK(Ca) 通道激活。BK(Ca) 通道和 PI3K 信号通路参与了 H(2)O(2)诱导的血管舒张，PI3K 通路诱导的 H(2)O(2) 血管舒张主要是由于调节 BK(Ca) 通道活性。
