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Enhanced calcium sensitivity of endothelial calcium‐activated large conductance potassium channels
Author(s) -
Riddle Melissa Anne,
Walker Benjimen R
Publication year - 2010
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.24.1_supplement.592.8
Subject(s) - iberiotoxin , bk channel , chemistry , calcium activated potassium channel , biophysics , conductance , potassium channel , calcium , patch clamp , endocrinology , medicine , membrane potential , receptor , biochemistry , biology , mathematics , organic chemistry , combinatorics
Chronic hypoxia (CH; 48 hr 0.5 atm) causes blunted arterial vasoconstriction in rats. Inhibition of endothelial cell (EC) heme oxygenase (HO) or large conductance Ca 2+ ‐ activated K + channels (BK) restores reactivity, but is without effect in controls. Further, BK currents in ECs from CH rats are inhibited by HO blockade, suggesting functional coupling of HO with BK channels. Since HO‐derived CO may enhance BK Ca 2+ sensitivity, we hypothesized that channels from CH ECs are more sensitive to Ca 2+ than BK channels from vascular smooth muscle (VSM) due to the tonic presence of CO. We performed patch clamp experiments on freshly dispersed aortic ECs in whole cell‐cell attached and inside‐out configurations to characterize BK. Small (SK) and intermediate (IK) conductance K + channels were detected in cells from each group. In contrast, iberiotoxin (IBTX)‐sensitive channels with unitary conductance of 146±10 pS/222±13 pS (asymmetrical/symmetrical K + ) were found only in ECs from CH rats. EC BK channels were more sensitive to Ca 2+ than SK and IK and had markedly greater Ca 2+ sensitivity than VSM BK. This enhanced Ca 2+ sensitivity may contribute to the apparent tonic activity of EC BK channels following CH.