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IKCa and SKCa channels modulate endothelial Ca2+ influx and vasorelaxation to carbachol but not ATP in mouse thoracic aorta
Author(s) -
Marrelli Sean P,
Carr Ryan M,
Kochukov Mikhail Y
Publication year - 2011
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.25.1_supplement.820.17
The role of membrane potential on endothelial cell (EC) Ca2+ regulation and subsequent vasorelaxation is unresolved. Intermediate and small conductance calcium‐sensitive potassium channels (IKCa & SKCa) are present in mouse aortic endothelium and promote EC hyperpolarization upon elevation of cytosolic Ca 2+ . We investigated the role of IKCa/SKCa channels in endothelial‐mediated vasorelaxation through purinergic and cholinergic receptor systems. Mouse thoracic aorta segments were mounted in an isometric tension bath, preconstricted to phenylephrine, and then relaxed to either ATP (10 uM) or carbachol (CCh, 0.3 uM). After washout, NS309 (IK/SKCa channel activator), Tram‐34 and UCL1684 (IKCa and SKCa channel blockers), or vehicle control was applied before a second relaxation response. Intracellular Ca 2+ ([Ca 2+ ] i ) was measured in primary cultures of aorta EC by fura 2. Relaxations to CCh were significantly attenuated or potentiated by IKCa/SKCa channel blockade or activation, respectively. Additionally, the EC [Ca 2+ ] i response was significantly prolonged by IK/SKCa channel activation. In contrast, modulation of IKCa/SKCa channels had no significant effect on ATP‐mediated relaxations or EC [Ca 2+ ] i . These data indicate that IK/SKCa channels can modulate endothelial‐mediated vasorelaxation through potentiation of EC Ca 2+ influx in some receptor systems, but not all. (NIH R01 HL088435 to SPM)