Biphasic effects of H₂O₂ on BK_Ca channels

Abstract

The inhibitory or activating effect of H₂O₂ 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 H₂O₂ inhibited BK_Ca channel activity in inside-out patches but enhanced BK_Ca channel activity in cell-attached patches. The inhibition by H₂O₂ 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 H₂O₂-induced BK_Ca channel activation in cell-attached patches. BK_Ca channels and PI3K signaling pathway were involved in H₂O₂-induced vasodilation and H₂O₂-induced vasodilation by PI3K pathway was mainly due to modulation of BK_Ca channel activity.

Keywords::

• BK_Ca channels
• H₂O₂
• cysteine
• PI3K
• vasodilation

Acknowledgements

We thank Professor J. P. Ding for plasmids and help in electrophysiology techniques.

Declaration of interest: This work was supported by National Natural Science Foundation of China (30500109). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This paper was first published online on Early Online on 22 June 2010.