Abstract
Big conductance calcium activated potassium(BK) channel plays a critical role in pathophysiological regulation of vascular function. Recent studies indicated that the expression reduction of BK channels in high glucose condition exacerbated vessel dilation, and led to coronary artery diseases, while BK channel expression was reserved in A-kinase anchoring protein(AKAP) knockout mice at same condition. Here, We are to investigate heterologous co-expression of Nedd4 ligase, ubiquitin protein ligase, and KCa1.1 in HEK293 cells. The result shown that co-expression reduced BK current density without modulation of kinetic properties as measured by path clamp techniques. Modulation of current density was dependent on ligase activity and was lost in AKAP knockout mice with diabetes mellitus. Taken together, our data disclose a novel mechanism of KCa1.1 channel regulation that NEDD4 decreased BK channels expression in diabetes mellitus depending on AKAP signal complexity. These findings provide a new insight into potential therapeutic target in vascular diseases, especially in diabetes mellitus.This work was supported by the National Natural Science Foundation of China(Grant No. 8137034)
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