Apelin-13 Inhibits Large-Conductance Ca2 -Activated K Channels in Cerebral Artery Smooth Muscle Cells via a PI3-Kinase Dependent MechanismReport as inadecuate




Apelin-13 Inhibits Large-Conductance Ca2 -Activated K Channels in Cerebral Artery Smooth Muscle Cells via a PI3-Kinase Dependent Mechanism - Download this document for free, or read online. Document in PDF available to download.

Apelin-13 causes vasoconstriction by acting directly on APJ receptors in vascular smooth muscle VSM cells; however, the ionic mechanisms underlying this action at the cellular level remain unclear. Large-conductance Ca2+-activated K+ BKCa channels in VSM cells are critical regulators of membrane potential and vascular tone. In the present study, we examined the effect of apelin-13 on BKCa channel activity in VSM cells, freshly isolated from rat middle cerebral arteries. In whole-cell patch clamp mode, apelin-13 0.001-1 μM caused concentration-dependent inhibition of BKCa in VSM cells. Apelin-13 0.1 µM significantly decreased BKCa current density from 71.25±8.14 pA-pF to 44.52±7.10 pA-pF n=14 cells, P<0.05. This inhibitory effect of apelin-13 was confirmed by single channel recording in cell-attached patches, in which extracellular application of apelin-13 0.1 µM decreased the open-state probability NPo of BKCa channels in freshly isolated VSM cells. However, in inside-out patches, extracellular application of apelin-13 0.1µM did not alter the NPo of BKCa channels, suggesting that the inhibitory effect of apelin-13 on BKCa is not mediated by a direct action on BKCa. In whole cell patches, pretreatment of VSM cells with LY-294002, a PI3-kinase inhibitor, markedly attenuated the apelin-13-induced decrease in BKCa current density. In addition, treatment of arteries with apelin-13 0.1 µM significantly increased the ratio of phosphorylated-Akt-total Akt, indicating that apelin-13 significantly increases PI3-kinase activity. Taken together, the data suggest that apelin-13 inhibits BKCa channel via a PI3-kinase-dependent signaling pathway in cerebral artery VSM cells, which may contribute to its regulatory action in the control of vascular tone.



Author: Amit Modgil , Lirong Guo , Stephen T. O’Rourke, Chengwen Sun

Source: http://plos.srce.hr/



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