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Hydrogen peroxide stimulates the Ca2+‐activated Big‐conductance K channels (BK) through cGMP signaling pathway in cultured human endothelial cells.
Author(s) -
Dong Deli,
Yue Peng,
Wang Wenhui
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1235.6
Subject(s) - bk channel , chemistry , nadph oxidase , ebselen , microbiology and biotechnology , biochemistry , biophysics , membrane potential , reactive oxygen species , biology , enzyme , glutathione , glutathione peroxidase
We used the whole cell patch‐clamp technique to examine the effect of H2O2 on BK channels in human endothelial cells. We confirmed the previous finding that a 200 pS BK channel activity was detected when the cell membrane potential was clamped at 50 mV. Application of H2O2 (100 micromole) or adding 1 unit glucose oxidase stimulated BK channels. The stimulatory effect of H2O2 and GO was absent in cells treated with 10 micromole ebselen, a scavenger of superoxide anions. To determine whether the stimulatory effect of H2O2 and GO on BK channels was the result of increasing NO production in the endothelial cells, we examined the effect of H2O2 and GO on BK channels in the presence of 0.1 mM L‐NAME which inhibits NO synthase (NOS). Inhibition of NOS completely abolished the stimulatory effect of H2O2 on BK channels. In contrast, treatment of endothelial cells with D‐NAME did not block the effect of H2O2 on BK channels. Moreover, inhibiting soluble guanylate cyclase (sGC) with ODQ mimicked the effect of L‐NAME and abolished the effect of H2O2. Also, inhibiting protein kinase G with KT5823 abolished the stimulatory effect of H2O2 on BK channels. We conclude that H2O2 stimulates BK channels through NO/sGC/cGMP pathway in the cultured human endothelial cells.