NYMC Faculty Publications
Angiotensin II Stimulates Basolateral 50-Ps K Channels in the Thick Ascending Limb
Author Type(s)
Faculty
DOI
10.1152/ajprenal.00476.2013
Journal Title
American Journal of Physiology. Renal Physiology
First Page
F509
Last Page
16
Document Type
Article
Publication Date
3-1-2014
Abstract
We used the patch-clamp technique to examine the effect of angiotensin II (ANG II) on the basolateral K channels in the thick ascending limb (TAL) of the rat kidney. Application of ANG II increased the channel activity and the current amplitude of the basolateral 50-pS K channel. The stimulatory effect of ANG II on the K channels was completely abolished by losartan, an inhibitor of type 1 angiotensin receptor (AT1R), but not by PD123319, an AT2R antagonist. Moreover, inhibition of phospholipase C (PLC) and protein kinase C (PKC) also abrogated the stimulatory effect of ANG II on the basolateral K channels in the TAL. This suggests that the stimulatory effect of ANG II on the K channels was induced by activating PLC and PKC pathways. Western blotting demonstrated that ANG II increased the phosphorylation of c-Src at tyrosine residue 416, an indication of c-Src activation. This effect was mimicked by PKC stimulator but abolished by calphostin C. Moreover, inhibition of NADPH oxidase (NOX) also blocked the effect of ANG II on c-Src tyrosine phosphorylation. The role of Src-family protein tyrosine kinase (SFK) in mediating the effect of ANG II on the basolateral K channel was further suggested by the experiments in which inhibition of SFK abrogated the stimulatory effect of ANG II on the basolateral 50-pS K channel. We conclude that ANG II increases basolateral 50-pS K channel activity via AT1R and that activation of AT1R stimulates SFK by a PLC-PKC-NOX-dependent mechanism.
Recommended Citation
Wang, M., Luan, H., Wu, P., Fan, L., Wang, L., Duan, X., Zhang, D., Wang, W., & Gu, R. (2014). Angiotensin II Stimulates Basolateral 50-Ps K Channels in the Thick Ascending Limb. American Journal of Physiology. Renal Physiology, 306 (5), F509-16. https://doi.org/10.1152/ajprenal.00476.2013