| First Author | Qian X | Year | 2014 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 34 |
| Issue | 1 | Pages | 127-35 |
| PubMed ID | 24177326 | Mgi Jnum | J:222833 |
| Mgi Id | MGI:5645648 | Doi | 10.1161/ATVBAHA.113.302506 |
| Citation | Qian X, et al. (2014) Positive feedback regulation of agonist-stimulated endothelial Ca2+ dynamics by KCa3.1 channels in mouse mesenteric arteries. Arterioscler Thromb Vasc Biol 34(1):127-35 |
| abstractText | OBJECTIVE: 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. APPROACH AND RESULTS: 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 mumol/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 mumol/L) and apamin (0.5 mumol/L) or transient receptor potential vanilloid 4 channels with HC-067047 (1 mumol/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. CONCLUSIONS: IK1, and to some extent SK3, channels exert a substantial positive feedback influence on endothelial Ca(2+) dynamics. |
