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

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 mu m) 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 Go6976, which inhibits Ca2+-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 F isoform of PKC. Western blot analysis confirmed that PKC alpha, and not PKC beta, 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 PKC alpha. (c) 2006 Elsevier Inc. All rights reserved.