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Endothelial KCa ion channels: their compartmentation in caveolae and relevance to cardiovascular pathologies
Author(s) -
Kaistha Anuradha,
Brähler Sebastian,
Kaistha Brajesh Pratap,
Wulff Heike,
Köhler Ralf,
Hoyer Joachim
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.784.3
Subject(s) - caveolae , endothelium , electrical impedance myography , caveolin 1 , endothelial dysfunction , stretch activated ion channel , ion channel , chemistry , acetylcholine , microbiology and biotechnology , endocrinology , medicine , biology , vasodilation , voltage gated ion channel , signal transduction , receptor
Ca2+‐activated K+‐channels KCa2.3 and KCa3.1 are expressed in caveolae rich endothelium and their activation plays an important role in EDHF‐dilations. Yet, specific localization of these channels and role in EDHF and hypertension are not fully understood. Here we characterized caveolar compartment to study localization of these channels in endothelium. Effect of caveolin‐1 loss on functioning of these channels was studied using Cav‐1 deficient mice, and furthermore, to clarify specific contributions of these channels, we generated mice deficient of both channels. Sucrose density gradient and immunofluorescence revealed differential localization of endothelial KCa2.3 and KCa3.1 channels into caveolar and non‐caveolar compartments, respectively. Pressure myography showed that KCa3.1 deficiency has severe impact on acetylcholine‐induced EDHF‐dilation, whereas KCa2.3 deficiency impairs shear stress dilation. KCa3.1/KCa2.3‐deficient mice exhibited elevated blood pressure, most prominent during physical activity, as determined by telemetry. Cav‐1 deficient mice, exhibited impaired EDHF‐dilations in response to both, Ach and shear stress. We conclude that these endothelial channels are important in the control of vascular tone and overall circulatory regulation. Loss of caveolae results in impaired functioning of these channels and thereby contributes to cardiovascular pathologies.