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- Title
Effects of Angiotensin II on sustained outward currents in rat ventricular myocytes.
- Authors
Matsuda, Hiroyuki; Kurata, Yasutaka; Imanishi, Sunao; Sato, Ryoichi; Shibamoto, Toshishige
- Abstract
We investigated the effects of angiotensin II (Ang II) on the sustained outward current (Isus) and action potential of rat ventricular myocytes using the whole-cell patch-clamp technique. Ang II at 30 nM~3 µM inhibited Isus with an IC50 of 240 nM, a Hill coefficient of 1.0 and maximum inhibition of 19.4%. Ang II-mediated inhibition of Isus was voltage independent, was due to a decrease in the K+ current and was abolished by the Ang II type-I (AT1) receptor blocker, valsartan. The protein kinase C (PKC) inhibitors PKC19–36 or calphostin C, abolished Ang II-mediated inhibition of Isus. In contrast, pretreatment with the protein kinase A (PKA) inhibitor PKA6–22 (100 µM) significantly enhanced the suppression of Isus by 1 µM Ang II: (33.7±5.1% vs. control 17.1±2.3%). These results indicate that Ang II inhibits Isus via the AT1 receptor and activation of PKC. Ang II significantly prolonged action potential duration (APD) when the control APD was lengthened by a Ca2+ channel activator, BAY K8644. In myocytes with a relatively long APD, Ang II may prolong APD by inhibiting Isus.
- Subjects
ANGIOTENSINS; HEART ventricles; PROTEIN kinases; MUSCLE cells; RESPONSE inhibition; LABORATORY rats
- Publication
Pflügers Archiv: European Journal of Physiology, 2004, Vol 448, Issue 1, p54
- ISSN
0031-6768
- Publication type
Article
- DOI
10.1007/s00424-003-1217-6