title: Angiotensin II inhibits inward rectifier K+ channels in rabbit coronary arterial smooth muscle cells through protein kinase Calpha.
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 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.
authors.affiliation: 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.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.forename: Jae Boum
authors.initials: JB
authors.lastname: Youm
authors.forename: Mohamad
authors.initials: M
authors.lastname: Warda
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Ko
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Kim
authors.forename: Yung E
authors.initials: YE
authors.lastname: Earm
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002413:Cations, Divalent / Q000737:chemistry; D002478:Cells, Cultured; D004594:Electrophysiology; D005260:Female; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000145:classification / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002413:Cations, Divalent; D007527:Isoenzymes; D024661:Potassium Channels, Inwardly Rectifying; D047428:Protein Kinase Inhibitors; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D051571:Protein Kinase C-alpha; D010738:Type C Phospholipases; D002118:Calcium