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Positive feedback influence of K Ca 3.1 channels on stimulated endothelial Ca 2+ dynamics
Author(s) -
Taylor Mark Stephen,
Köhler Ralf,
Michael Francis,
Qian Xun
Publication year - 2013
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.27.1_supplement.901.13
Subject(s) - hyperpolarization (physics) , chemistry , vasodilation , acetylcholine , endothelium , extracellular , biophysics , endocrinology , medicine , membrane potential , biology , biochemistry , stereochemistry , nuclear magnetic resonance spectroscopy
Dynamic Ca 2+ transients underlie physiologic endothelial signaling and vasoregulation. Intermediate conductance Ca 2+ ‐activated K + channels (K Ca 3.1) are primary targets of endothelial Ca 2+ signals in the arterial vasculature and their ablation results in hypertension. Localized Ca 2+ events target K Ca 3.1 channels along the myoendothelial interface to elicit hyperpolarization and vasodilation. Here, we employ genetically altered K Ca 3.1 knockout mice (IK1 −/− ), confocal imaging, and custom analysis to assess possible feedback influence of these channels on the Ca 2+ dynamics themselves. Basal endothelial Ca 2+ dynamics were not different between IK1 −/− and wild‐type (WT) mice (p < 0.05). However, acetylcholine (Ach) stimulated Ca 2+ dynamics to a much greater degree in WT than in IK1 −/− endothelium (sites 376 vs. 156; p < 0.05). Removal of extracellular Ca 2+ reduced Ach‐induced Ca 2+ dynamics in WT to the level of IK1 −/− . These findings indicate that whereas K Ca 3.1 channels do not directly influence basal Ca 2+ activity in mouse mesenteric artery endothelium, they exert substantial positive feedback under stimulated conditions, recruiting additional new Ca 2+ sites and events along the intima. Overall, our findings suggest that K Ca 3.1 channels amplify endothelial Ca 2+ dynamics, further enhancing arterial hyperpolarization and vasodilation. Supported by NIH R01 HL085887 and S10RR027535.