Angiotensin II inhibits inward rectifier K+ channels in rabbit coronary arterial smooth muscle cells through protein kinase Calpha.
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.
Park
Won Sun
WS
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.
Kim
Nari
N
Youm
Jae Boum
JB
Warda
Mohamad
M
Ko
Jae-Hong
JH
Kim
Sung Joon
SJ
Earm
Yung E
YE
Han
Jin
J
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
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