title: Endothelin-1 inhibits inward rectifier K+ channels in rabbit coronary arterial smooth muscle cells through protein kinase C.
abstract: We studied inward rectifier K+ (Kir) channels in smooth muscle cells isolated from rabbit coronary arteries. In cells from small- (<100 microm, SCASMC) and medium-diameter (100 approximately 200 microm, MCASMC) coronary arteries, Kir currents were clearly identified (11.2 +/- 0.6 and 4.2 +/- 0.6 pA pF at -140 mV in SCASMC and MCASMC, respectively) that were inhibited by Ba(2+) (50 microm). By contrast, a very low Kir current density (1.6 +/- 0.4 pA pF) was detected in cells from large-diameter coronary arteries (>200 microm, LCASMC). The presence of Kir2.1 protein was confirmed in SCASMC in a Western blot assay. Endothelin-1 (ET-1) inhibited Kir currents in a dose-dependent manner. The inhibition of Kir currents by ET-1 was abolished by pretreatment with the protein kinase C (PKC) inhibitor staurosporine (100 nM) or GF 109203X (1 microm). The PKC activators phorbol 12,13-dibutyrate (PDBu) and 1-oleoyl-2-acetyl-sn-glycerol (OAG) reduced Kir currents. The ETA-receptor inhibitor BQ-123 prevented the ET-1-induced inhibition of Kir currents. The amplitudes of the ATP-dependent K+ (KATP), Ca(2+)-activated K+ (BKCa), and voltage-dependent K+ (KV) currents, and effects of ET-1 on these channels did not differ between SCASMC and LCASMC. From these results, we conclude that Kir channels are expressed at a higher density in SCASMC than in larger arteries and that the Kir channel activity is negatively regulated by the stimulation of ETA-receptors via the PKC pathway.
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, Korea.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.forename: Jae Boum
authors.initials: JB
authors.lastname: Youm
authors.forename: Hyun
authors.initials: H
authors.lastname: Joo
authors.forename: Hyung Kyu
authors.initials: HK
authors.lastname: Kim
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Ko
authors.forename: Yung E
authors.initials: YE
authors.lastname: Earm
mesh_terms: D000818:Animals; D001464:Barium / Q000494:pharmacology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors*; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits
chemical_list: D019332:Endothelin-1; D024661:Potassium Channels, Inwardly Rectifying; D001464:Barium; D011493:Protein Kinase C