Angiotensin II inhibits inward rectifier K+ channels in rabbit coronary arterial smooth muscle cells through protein kinase Cα

Abstract

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 μm) 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 Ca2+ free condition and by Gö6976, which inhibits Ca2+-dependent PKC isoforms α and β. However, the inhibitory effect of Ang II was unaffected by a peptide that selectively inhibits the translocation of the ε isoform of PKC. Western blot analysis confirmed that PKCα, and not PKCβ, 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 AT1 receptors by the activation of PKCα. © 2006 Elsevier Inc. All rights reserved.