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

Abstract

The vasoconstrictor angiotensin II (ANG II) inhibits several types of K+ channels. We examined the inhibitory mechanism of ANG II on voltage-gated K+ (KV) currents ( I KV ) recorded from isolated rat arterial smooth muscle using patch-clamp techniques. Application of 100 nM ANG II accelerated the activation of I KV but also caused inactivation. These effects were abolished by the AT1 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 KV . 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 Ca2+-dependent PKC inhibitor Gö6976 (1 μM) but was abolished in the presence of 40 μM PKC-ε translocation inhibitor peptide. These results demonstrate that ANG II inhibits KVchannels through both activation of PKC-ε and inhibition of PKA.