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H 2 O 2 dilates human coronary arterioles by stimulating the large‐conductance Ca 2+ ‐activated K + channel activity
Author(s) -
Zhang David,
Mendoza Suelhem A.,
Gebremedhin Debebe,
Gutterman David D.
Publication year - 2011
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.25.1_supplement.1093.5
Subject(s) - iberiotoxin , vasodilation , conductance , arteriole , coronary artery disease , chemistry , contraction (grammar) , dilation (metric space) , western blot , patch clamp , potassium channel , medicine , calcium activated potassium channel , endothelium , artery , charybdotoxin , cardiology , biophysics , electrophysiology , biology , biochemistry , microcirculation , gene , geometry , mathematics , combinatorics
H 2 O 2 serves as an important endothelium‐derived vasodilator factor in human coronary arterioles (HCAs) from patients with coronary artery disease (CAD). The cellular mechanisms by which H 2 O 2 dilates HCAs remain unclear. Here we investigated the potential role of large‐conductance Ca 2+ ‐activated K + (BK Ca ) channels in the dilatory response to H 2 O 2 . Using RT‐PCR and immunocytochemistry, the expression of BK Ca was detected at both mRNA and protein levels in smooth muscle cells (SMCs) of HCAs. Western blot analysis of isolated arterioles revealed a higher level of BK Ca (the pore‐forming α subunit) protein expression in patients with CAD, as compared with those without CAD. Patch‐clamp analysis identified a voltage‐ and paxilline‐sensitive K + current with a unitary conductance of 240‐pS in freshly isolated coronary SMCs. Addition of H 2 O 2 (50 μM) in the bath solution significantly activated this K + current recorded from cell‐attached patches (NPo, 0.089±0.043 vs. 0.0043±0.0037 of baseline; n=3), an effect that was subsequently blocked by paxilline (0.0035±0.0035; n=3). In isolated endothelium‐denuded HCAs from CAD patients, H 2 O 2 elicited a concentration‐dependent dilation (dilation at 10 −4 M, 98±2%; n=3). This dilation was markedly inhibited by paxilline (40±10%; n=3). In conclusion, the BK Ca channel plays a key role in H 2 O 2 ‐induced dilation of HCAs in disease.