Angiotensin II inhibits and alters kinetics of voltage-gated K+ channels of rat arterial smooth muscle

• Published in: American journal of physiology. Heart and circulatory physiology 2001-12, Vol.281 (6), p.H2480-H2489
• Main Authors: Hayabuchi, Y, Standen, N. B, Davies, N. W
• Format: Article
• Language: English
• Subjects: Angiotensin II - pharmacology; Animals; Antihypertensive Agents - pharmacology; Cyclic AMP - analogs & derivatives; Cyclic AMP - pharmacology; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic AMP-Dependent Protein Kinases - metabolism; Diglycerides - pharmacology; Enzyme Inhibitors - pharmacology; Isoenzymes - antagonists & inhibitors; Isoenzymes - metabolism; Kinetics; Losartan - pharmacology; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mesenteric Arteries - cytology; Mesenteric Arteries - metabolism; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - enzymology; Patch-Clamp Techniques; Peptides - pharmacology; Potassium Channels, Voltage-Gated - metabolism; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Protein Kinase C-epsilon; Rats; Rats, Wistar; Thionucleotides - pharmacology; Vasoconstrictor Agents - pharmacology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.2001.281.6.h2480

Ion Channel Group, Department of Cell Physiology and Pharmacology, University of Leicester, Leicester LE1 9HN, United Kingdom The vasoconstrictor angiotensin II (ANG II) inhibits several types of K + channels. We examined the inhibitory mechanism of ANG II on voltage-gated K + (K V ) currents ( I K V ) recorded from isolated rat arterial smooth muscle using patch-clamp techniques. Application of 100 nM ANG II accelerated the activation of I K V but also caused inactivation. These effects were abolished by the AT 1 receptor antagonist losartan. The protein kinase A (PKA) inhibitor Rp-cyclic 3',5'-hydrogen phosphothioate adenosine (100 µM) and an analog of diacylglycerol, 1,2-dioctanyoyl-rac-glycerol (2 µM), caused a significant reduction of I K V . Furthermore, the combination of 5 µM PKA inhibitor peptide 5-24 (PKA-IP) and 100 µM protein kinase C (PKC) inhibitor peptide 19-27 (PKC-IP) prevented the inhibition by ANG II, although neither alone was effective. The ANG II effect seen in the presence of PKA-IP remained during addition of the Ca 2+ -dependent PKC inhibitor Gö6976 (1 µM) but was abolished in the presence of 40 µM PKC- translocation inhibitor peptide. These results demonstrate that ANG II inhibits K V channels through both activation of PKC- and inhibition of PKA. potassium channel; activation; inactivation; protein kinase A; protein kinase C