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Endothelial modulation of swine coronary artery tone through coupling of basal IP3R‐dependent Ca2+ signals to endothelial SK and IK channels
Author(s) -
Francis Michael,
Solodushko Viktoriya,
Taylor Mark S
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.1032.10
Subject(s) - apamin , charybdotoxin , hyperpolarization (physics) , endothelium , ryanodine receptor , medicine , iberiotoxin , chemistry , artery , biophysics , endocrinology , receptor , biology , potassium channel , organic chemistry , nuclear magnetic resonance spectroscopy
Basal Ca 2+ events originate from IP 3 receptors (IP 3 R) at distinct sites in endothelial cells leading to stimulation of membrane Ca 2+ ‐activated K + channels (K Ca ). Persistent activation of small (SK) and intermediate (IK) conductance K Ca channels may provide the foundation of endothelium derived hyperpolarization (EDH) in many vascular beds. Here we investigate the role of IP 3 ‐mediated Ca 2+ signaling through SK or IK channels in endothelial modulation of sustained coronary artery tone. In arteries pre‐contracted with U46619, the SK channel blocker apamin and the IK channel blocker charybdotoxin increased tone by 28.2% and 40.0%, respectively. These effects were endothelium dependent and were completely blocked by pretreatment with IP 3 R inhibitors xestospongin C or 2APB but not by ryanodine. Confocal imaging revealed dynamic endothelial Ca 2+ events emanating from distinct spots along the basolateral membrane. Immunostaining in the same vessels showed endothelial expression of all three IP 3 R isoforms with discrete distribution profiles. Our findings indicate basal endothelial IP 3 R Ca 2+ signals continuously modify coronary artery tone through constitutive SK and IK dependent hyperpolarization and relaxation. A working deterministic model was generated relating the density and distribution of specific endothelial IP 3 Rs to the origination and dynamics of Ca 2+ events in coronary artery endothelium.