Channelpedia

PubMed 24177326


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav2.3 , Cav3.1 , SK3 , SK4



Title: Positive feedback regulation of agonist-stimulated endothelial Ca2+ dynamics by KCa3.1 channels in mouse mesenteric arteries.

Authors: Xun Qian, Michael Francis, Ralf Köhler, Viktoriya Solodushko, Mike Lin, Mark S Taylor

Journal, date & volume: Arterioscler. Thromb. Vasc. Biol., 2014 Jan , 34, 127-35

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24177326


Abstract
Intermediate and small conductance KCa channels IK1 (KCa3.1) and SK3 (KCa2.3) are primary targets of endothelial Ca(2+) signals in the arterial vasculature, and their ablation results in increased arterial tone and hypertension. Activation of IK1 channels by local Ca(2+) transients from internal stores or plasma membrane channels promotes arterial hyperpolarization and vasodilation. Here, we assess arteries from genetically altered IK1 knockout mice (IK1(-/-)) to determine whether IK1 channels exert a positive feedback influence on endothelial Ca(2+) dynamics.Using confocal imaging and custom data analysis software, we found that although the occurrence of basal endothelial Ca(2+) dynamics was not different between IK1(-/-) and wild-type mice (P>0.05), the frequency of acetylcholine-stimulated (2 μmol/L) Ca(2+) dynamics was greatly decreased in IK1(-/-) endothelium (515±153 versus 1860±319 events; P<0.01). In IK1(-/-)/SK3(T/T) mice, ancillary suppression (+Dox) or overexpression (-Dox) of SK3 channels had little additional effect on the occurrence of events under basal or acetylcholine-stimulated conditions. However, SK3 overexpression did restore the decreased event amplitudes. Removal of extracellular Ca(2+) reduced acetylcholine-induced Ca(2+) dynamics to the same level in wild-type and IK1(-/-) arteries. Blockade of IK1 and SK3 with the combination of charybdotoxin (0.1 μmol/L) and apamin (0.5 μmol/L) or transient receptor potential vanilloid 4 channels with HC-067047 (1 μmol/L) reduced acetylcholine Ca(2+) dynamics in wild-type arteries to the level of IK1(-/-)/SK3(T/T)+Dox arteries. These drug effects were not additive.IK1, and to some extent SK3, channels exert a substantial positive feedback influence on endothelial Ca(2+) dynamics.