Voltage-dependent inhibition of the delayed outward potassium current by OPC-8490, a novel positive inotropic agent, in isolated atrial myocytes of guinea-pig heart

Author(s):  
Yoshihisa Kurachi ◽  
Yukio Asano ◽  
Hiroyuki Ito ◽  
Tsuneaki Sugimoto
1999 ◽  
Vol 277 (1) ◽  
pp. H119-H127 ◽  
Author(s):  
Michael Dittrich ◽  
Jürgen Daut

Capillary fragments were isolated from guinea pig hearts, and their electrical properties were studied using the perforated-patch and cell-attached mode of the patch-clamp technique. A voltage-dependent K+ current was discovered that was activated at potentials positive to −20 mV and showed a sigmoid rising phase. For depolarizing voltage steps from −128 to +52 mV, the time to peak was 71 ± 5 ms (mean ± SE) and the amplitude of the current was 3.7 ± 0.5 pA/pF in the presence of 5 mM external K+. The time course of inactivation was exponential with a time constant of 7.2 ± 0.5 s at +52 mV. The current was blocked by tetraethylammonium (inhibitory constant ∼3 mM) but was not affected by charybdotoxin (1 μM) or apamin (1 μM). In the cell-attached mode, depolarization-activated single-channel currents were found that inactivated completely within 30 s; the single-channel conductance was 12.3 ± 2.4 pS. The depolarization-activated K+current described here may play a role in membrane potential oscillations of the endothelium.


2000 ◽  
Vol 23 (11P2) ◽  
pp. 1812-1815 ◽  
Author(s):  
BODO BRANDTS ◽  
MARC VAN BRACHT ◽  
FRANK TÜTTELMANN ◽  
MAURITZ A. ALLESSIE ◽  
HANS-JOACHIM TRAPPE

2003 ◽  
Vol 14 (6) ◽  
pp. 621-631 ◽  
Author(s):  
Mark Warren ◽  
Prabal K. Guha ◽  
Omer Berenfeld ◽  
Alexey Zaitsev ◽  
Justus M.B. Anumonwo ◽  
...  

Author(s):  
Leonid Tyan ◽  
Daniel Turner ◽  
Karlie R Komp ◽  
Roman Y Medvedev ◽  
Evi Lim ◽  
...  

Angiotensin II (AngII) is a key mediator of the renin-angiotensin system and plays an important role in the regulation of cardiac electrophysiology by affecting various cardiac ion currents, including transient outward potassium current Ito. AngII receptors and molecular components of Ito, Kv4.2 and Kv4.3 channels, have been linked to caveolae structures. However, their functional interaction as well as the importance of such proximity within 50-100nm caveolar nanodomains, remain unknown. To address this, we studied the mechanisms of Ito regulation by AngII in atrial myocytes of wild type (WT) and cardiac-specific caveolin-3 (Cav3) conditional knock-out (Cav3KO) mice. We showed that in WT atrial myocytes, a short-term (2 hours) treatment with AngII (5 µM) significantly reduced Ito density. This effect was prevented (1) by a 30-min pretreatment with a selective antagonist of AngII receptor 1 (Ang1R) losartan (2 µM) or (2) by a selective inhibition of protein kinase C (PKC) by BIM1 (10 µM). The effect of AngII on Ito was completely abolished in Cav3-KO mice, with no change in a baseline Ito current density. In WT atria, Ang1Rs co-localized with Cav3, and the expression of Ang1Rs was significantly decreased in Cav3KO in comparison with WT mice while no change in Kv4.2 and Kv4.3 protein expression was observed. Overall, our findings demonstrate that Cav3 is involved in the regulation of Ang1R expression and is required for modulation of Ito by AngII in mouse atrial myocytes.


2000 ◽  
Vol 129 (4) ◽  
pp. 695-702 ◽  
Author(s):  
A V Zholos ◽  
Ya D Tsytsyura ◽  
I B Philyppov ◽  
M F Shuba ◽  
T B Bolton

1994 ◽  
Vol 64 ◽  
pp. 307
Author(s):  
Kageyoshi Ono ◽  
Koji Eto ◽  
Aiji Sakamoto ◽  
Gozoh Tsujimoto ◽  
Motoyoshi Satake

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