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Endothelial Large‐conductance Calcium Activated Potassium (BK Ca ) Channels And Pulmonary Endothelial Function
Author(s) -
Choudhary Gaurav,
Vang Alexander,
Newton Julie,
Rounds Sharon
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.797.3
Subject(s) - bk channel , chemistry , calcium activated potassium channel , endothelium , acetylcholine , phenylephrine , biophysics , charybdotoxin , iberiotoxin , vasodilation , potassium channel , calcium , medicine , membrane potential , biochemistry , biology , blood pressure , organic chemistry
We hypothesized that endothelial BK Ca channel activation can improve pulmonary endothelial function by causing change in membrane potential (E m ), [Ca 2+ ] i and NO release. Methods Lung microvascular endothelial cell (EC) E m , [Ca 2+ ] i and NO change was measured using fluorescence imaging with DiBAC4(3), Fura‐2AM and DAF‐FM, respectively. Phenylephrine preconstricted pulmonary arterial (PA) rings were used to assay the effect of acetylcholine (Ach) on vessel relaxation. PA pressures were monitored in preconstriced isolated ventilated‐perfused rat lungs (IPL) after BK Ca channels activation. Results BK Ca channels were demonstrated in macro‐ and microvascular endothelium by immunohistochemistry in rat lungs and by immunoblot in EC lysates. BK Ca channel activation with 30μM NS1619 led to endothelial hyperpolarization and an increase in [Ca 2+ ] i and NO. Also, NS1619 caused enhanced endothelium‐dependent dilation in PA rings, with no effect on endothelium‐independent dilation using NO donor or endothelium‐denuded rings. K + channel blocker, TEA, abolished the effect of NS1619 on endothelium dependent dilation. In IPL, BK Ca channel activation by NS1619 caused a dose‐dependent reduction in PA pressures that was attenuated by the inhibition of NO production. Conclusion Pulmonary EC express BK Ca channels. Activation of pulmonary endothelial BK Ca channels leads to improvement in endothelial function.