Angiotensin II inhibits rat arterial K-ATP channels by inhibiting steady-state protein kinase A activity and activating protein kinase Ca

Citation
Y. Hayabuchi et al., Angiotensin II inhibits rat arterial K-ATP channels by inhibiting steady-state protein kinase A activity and activating protein kinase Ca, J PHYSL LON, 530(2), 2001, pp. 193-205
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Physiology
Journal title
JOURNAL OF PHYSIOLOGY-LONDON
ISSN journal
0022-3751 → ACNP
Volume
530
Issue
2
Year of publication
2001
Pages
193 - 205
Database
ISI
SICI code
0022-3751(20010115)530:2<193:AIIRAK>2.0.ZU;2-R
Abstract
1. We used whole-cell patch clamp to investigate steady-state activation of ATP-sensitive K+ channels (K-ATP) of rat arterial smooth muscle by protein kinase A (PKA) and the pathway by which angiotensin II (Ang II) inhibits t hese channels. 2. Rp-cAMPS, an inhibitor of PKA, did not affect K-ATP currents activated b y pinacidil when the intracellular solution contained 0.1 mM ATP. However, when ATP was increased to 1.0 mM, inhibition of PKA reduced K-ATP current, while the phosphatase inhibitor calyculin A caused a small increase in curr ent. 3. Ang II (100 nM) inhibited K-ATP current activated by the K+ channel open er pinacidil. The degree of inhibition was greater with 1.0 mM than with 0. 1 mM intracellular ATP. The effect of Ang II was abolished by the AT(1) rec eptor antagonist losartan. 4. The inhibition of K-ATP currents by Ang II was abolished by a, combinati on of PKA inhibitor peptide 5-24 (5 muM) and PKC inhibitor peptide 19-27 (1 00 muM), while either alone caused only partial block of the effect. 5. In the presence of PKA inhibitor peptide, the inhibitory effect of Ang I I was unaffected by the PKC inhibitor Go 6976, which is selective for Ca2+- dependent isoforms of PKC, but was abolished by a selective peptide inhibit or of the translocation of the epsilon isoform of PKC. 6. Our results indicate that K-ATP channels are activated by steady-state p hosphorylation by PKA at normal intracellular ATP levels, and that Ang II i nhibits the channels both through activation of PKC epsilon and inhibition of PKA.