Endothelin-1 inhibits inward rectifier K+ channels in rabbit coronary arterial smooth muscle cells through protein kinase C

• Published in: Journal of cardiovascular pharmacology Vol. 46; no. 5; p. 681
• Main Authors: Park, Won Sun, Han, Jin, Kim, Nari, Youm, Jae Boum, Joo, Hyun, Kim, Hyung Kyu, Ko, Jae-Hong, Earm, Yung E
• Format: Journal Article
• Language: English
• Published: United States 01.11.2005
• Subjects: Animals; Barium - pharmacology; Cells, Cultured; Coronary Vessels - cytology; Coronary Vessels - drug effects; Coronary Vessels - metabolism; Endothelin-1 - pharmacology; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Patch-Clamp Techniques; Potassium Channels, Inwardly Rectifying - antagonists & inhibitors; Protein Kinase C - metabolism; Rabbits
• ISSN: 0160-2446
• DOI: 10.1097/01.fjc.0000182846.08357.ed

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.