S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Physiology (생리학교실) Journal Papers (저널논문_생리학교실)
Angiotensin II inhibits inward rectifier K+ channels in rabbit coronary arterial smooth muscle cells through protein kinase Calpha
- Park, Won Sun; Kim, Nari; Youm, Jae Boum; Warda, Mohamad; Ko, Jae-Hong; Kim, Sung Joon; Earm, Yung E.; Han, Jin
- Issue Date
- Biochem Biophys Res Commun. 2006 Mar 17;341(3):728-35. Epub 2006 Jan 19.
- Angiotensin II/*pharmacology; Animals; Calcium/chemistry/metabolism; Cations, Divalent/chemistry; Cells, Cultured; Electrophysiology; Female; Isoenzymes/antagonists & inhibitors/classification/metabolism; Male; Muscle, Smooth, Vascular/*drug effects/*metabolism; Myocytes, Smooth Muscle/*drug effects/*metabolism; Patch-Clamp Techniques; Potassium Channels, Inwardly Rectifying/*metabolism; Protein Kinase C-alpha/antagonists & inhibitors/*metabolism; Protein Kinase Inhibitors/pharmacology; Rabbits; Receptor, Angiotensin, Type 1/metabolism; Type C Phospholipases/antagonists & inhibitors/metabolism
- We investigated the effects of the vasoconstrictor angiotensin (Ang) II on the whole cell inward rectifier K(+) (Kir) current enzymatically isolated from small-diameter (<100 microm) coronary arterial smooth muscle cells (CASMCs). Ang II inhibited the Kir current in a dose-dependent manner (half inhibition value: 154 nM). Pretreatment with phospholipase C inhibitor and protein kinase C (PKC) inhibitors prevented the Ang II-induced inhibition of the Kir current. The PKC activator reduced the Kir currents. The inhibitory effect of Ang II was reduced by intracellular and extracellular Ca(2+) free condition and by Go6976, which inhibits Ca(2+)-dependent PKC isoforms alpha and beta. However, the inhibitory effect of Ang II was unaffected by a peptide that selectively inhibits the translocation of the epsilon isoform of PKC. Western blot analysis confirmed that PKCalpha, and not PKCbeta, was expressed in small-diameter CASMCs. The Ang II type 1 (AT(1))-receptor antagonist CV-11974 prevented the Ang II-induced inhibition of the Kir current. From these results, we conclude that Ang II inhibits Kir channels through AT(1) receptors by the activation of PKCalpha.
- 0006-291X (Print)
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