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Hydrogen peroxide increases cerebral arterial KCa channel opening through activation of Akt signaling pathway
Author(s) -
Gebremedhin Debebe,
Maia Terashvili,
Harder David R
Publication year - 2009
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.23.1_supplement.617.20
Subject(s) - wortmannin , ly294002 , chemistry , hydrogen peroxide , protein kinase b , biophysics , pi3k/akt/mtor pathway , microbiology and biotechnology , signal transduction , biochemistry , biology
The oxidant hydrogen peroxide (H 2 O 2 ) is not only an inducer of cellular damage, but can also play a role as a modulator of vascular function. Exogenous application of H 2 O 2 (3‐300 µM) resulted in a concentration‐dependent increase in NPo of K Ca single‐channel currents recorded from cell attached patches at a patch potential of +40 mV, whereas this oxidant did not change the NPo of K Ca single‐channel current when recorded from excised inside‐out membrane patches of cerebral arterial muscle cells (CAMCs). The membrane permeant organic peroxide tert ‐butyl hydroperoxide ( t ‐BOOH) (30 µM) also induced similar increase in NPo of K Ca single‐channel currents in the cell‐attached patches but had no effect on NPo of the single‐channel K Ca currents recorded from excised inside‐out patches at a the same patch potential. In an attempt to elucidate possible signaling mechanism mediating the effects of these oxidants on K Ca channel currents in CAMCs, we examined the impact of inhibition of the phospoinositide 3‐kinase‐Akt (PI3K‐Akt) pathway on the stimulatory actions of both H 2 O 2 and t‐BOOH on K Ca channel current. Pretreatment of CAMCs with two structurally different PI3K‐Akt pathway inhibitors wortmannin (10 nM) and LY294002 (5 µM) significantly attenuated the H 2 O 2 ‐ or t‐BOOH‐induced increase in NPo of single‐channel K Ca currents in CAMCs. On the other hand, stimulation of cerebral arterial muscle with either H 2 O 2 or t‐BOOH for 10 minutes induced activation of Akt as determined by western blot analysis. These findings suggest that activation of the Akt signaling pathway contributes to the H 2 O 2 ‐or t‐BOOH‐induced enhancement of K Ca channel currents in cerebral arterial muscle cells.