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

Citation
Y. Hayabuchi et al., Angiotensin II inhibits and alters kinetics of voltage-gated K+ channels of rat arterial smooth muscle, AM J P-HEAR, 281(6), 2001, pp. H2480-H2489
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
ISSN journal
0363-6135 → ACNP
Volume
281
Issue
6
Year of publication
2001
Pages
H2480 - H2489
Database
ISI
SICI code
0363-6135(200112)281:6<H2480:AIIAAK>2.0.ZU;2-Y
Abstract
The vasoconstrictor angiotensin II (ANG II) inhibits several types of K+ ch annels. 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 us ing patch-clamp techniques. Application of 100 nM ANG II accelerated the ac tivation of I-K V but also caused inactivation. These effects were abolishe d by the AT(1) receptor antagonist losartan. The protein kinase A (PKA) inh ibitor Rp-cyclic 3',5'-hydrogen phosphothioate adenosine (100 muM) and an a nalog of diacylglycerol, 1,2-dioctanyoyl-rac-glycerol (2 muM), caused a sig nificant reduction of I-K V. Furthermore, the combination of 5 muM PKA inhi bitor peptide 5-24 (PKA-IP) and 100 muM protein kinase C (PKC) inhibitor pe ptide 19-27 (PKC-IP) prevented the inhibition by ANG II, although neither a lone was effective. The ANG II effect seen in the presence of PKA-IP remain ed during addition of the Ca2+-dependent PKC inhibitor Go6976 (1 muM) but w as abolished in the presence of 40 muM PKC-epsilon translocation inhibitor peptide. These results demonstrate that ANG II inhibits K-V channels throug h both activation of PKC-epsilon and inhibition of PKA.