Flow Sensitivity of Inwardly-Rectifying K+ Channels in Human Aotic Endothelium

Y. Fang, V. Romanenko, P.F. Davies, and I. Levitan (USA)


hemodynamic forces, K channels, endothelium


Inwardly-rectifying K channels (Kir) dominate conductance in aortic endothelial cells and sensitivity of these channels to flow is suggested to play an important role in endothelial mechanotransduction. This is the first study to demonstrate flow sensitivity of Kir channels in human aortic endothelial cells (HAECs). As expected, flow-induced increase in Kir current density was accompanied by membrane hyperpolarization. Importantly, flow-induced increase in Kir was significantly suppressed when the cells were enriched with cholesterol suggesting that a loss of the flow sensitivity of endothelial Kir channels may contribute to impairment of endothelial function under hypercholesterolemic conditions. Finally, we show here that while endogenous endothelial Kir current increased upon the application of flow, the activity of the channels expressed in a null cell line were inhibited by flow application suggesting that the flow sensitivity of Kir channels depends critically on their cellular environment .

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