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Exploiting the cellular actions of SKCa and IKCa channels to manipulate endothelial function and vascular tone
Author(s) -
Braun Andrew P,
Sheng Jianzhong,
Ella Srikanth,
Davis Michael J,
Hill Michael A
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.627.6
Subject(s) - chemistry , iberiotoxin , vasodilation , apamin , hyperpolarization (physics) , bk channel , cremaster muscle , biophysics , nitric oxide , sk channel , calcium activated potassium channel , charybdotoxin , potassium channel , membrane potential , microcirculation , medicine , endocrinology , ion channel , biochemistry , biology , receptor , stereochemistry , organic chemistry , nuclear magnetic resonance spectroscopy
Growing evidence indicates that small‐ and intermediate‐conductance, Ca 2+ ‐activated K + channels (SK Ca and IK Ca channels, respectively) play pivotal roles in the cellular mechanisms contributing to stimulated vasorelaxation (i.e. nitric oxide (NO) synthesis, actions of EDHF). Using single cell patch clamp and fluorimetry, along with arteriolar pressure myography, we have obtained novel results demonstrating that activators of SK Ca and IK Ca channels (i.e. NS309 and DCEBIO, 0.01 ‐ 1 μM) enhance a number of cellular processes associated with stimulated vasorelaxation (i.e. cytosolic Ca 2+ elevations, membrane hyperpolarization and NO synthesis). These observed effects of NS309 and DCEBIO were largely prevented by the SK Ca and IK Ca channel blockers apamin and TRAM‐34 in combination, but not when applied separately. In rat cremaster arterioles pressurized to 70 mmHg, NS309 and DCEBIO reduced myogenic tone and further augmented ACh‐induced vasodilation. The eNOS inhibitor L‐NAME (0.1 mM) decreased ACh‐evoked inhibition of myogenic tone, but did not affect the dilatory responses to NS309 and DCEBIO. The observed inhibition of NS309/DCEBIO action following endothelial denudation confirmed that these agents acted predominantly via the vascular endothelium. Finally, we will discuss initial efforts to discern the contribution of STIM1 to SK Ca and IK Ca activity and endothelial vasodilatory processes.