Park Won Sun, Kim Nari, Youm Jae Boum, Warda Mohamad, Ko Jae-Hong, Kim Sung Joon, Earm Yung E, Han Jin
Mitochondrial Signaling Laboratory, Department of Physiology and Biophysics, College of Medicine, Biohealth Products Research Center, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Republic of Korea.
Biochem Biophys Res Commun. 2006 Mar 17;341(3):728-35. doi: 10.1016/j.bbrc.2006.01.026. Epub 2006 Jan 19.
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 Gö6976, 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.
我们研究了血管收缩剂血管紧张素（Ang）II对从小直径（<100微米）冠状动脉平滑肌细胞（CASMCs）酶法分离得到的全细胞内向整流钾（Kir）电流的影响。Ang II以剂量依赖性方式抑制Kir电流（半数抑制值：154 nM）。用磷脂酶C抑制剂和蛋白激酶C（PKC）抑制剂预处理可防止Ang II诱导的Kir电流抑制。PKC激活剂可降低Kir电流。在细胞内和细胞外无钙条件下以及用抑制钙依赖性PKC同工型α和β的Gö6976处理后，Ang II的抑制作用减弱。然而，Ang II的抑制作用不受选择性抑制PKCε同工型易位的肽的影响。蛋白质印迹分析证实，PKCα而非PKCβ在小直径CASMCs中表达。血管紧张素II 1型（AT(1)）受体拮抗剂CV-11974可防止Ang II诱导的Kir电流抑制。从这些结果，我们得出结论，Ang II通过激活PKCα，经由AT(1)受体抑制Kir通道。
