Effects of hydrogen peroxide on the transient outward current in rabbit atrial myocytes.
1. In the present study, we investigated the effects of hydrogen peroxide (H2O2) on the 4-aminopyridine-sensitive transient outward current (I(TO)) in rabbit atrial myocytes using the amphotericin B-perforated patch voltage-clamp method. 2. Superfusion of myocytes with H2O2 at 100 micromol/L gradually slowed the time-course of inactivation of I(TO) and increased the peak by 9% (n = 9). The H2O2-induced slowing of I(TO) inactivation was concentration dependent (over the concentration range 10 micromol/L to 1 mmol/L). These effects were hardly reversed by washout of H2O2, but were quickly abolished by dithiothreitol (2 mmol/L). 3. Bisindolylmaleimide (100 nmol/L), an inhibitor of protein kinase C, significantly attenuated the H2O2-induced effects on I(TO). 4. These results suggest that rabbit atrial I(TO) is susceptible to oxidation by H2O2 at concentrations relevant to those encountered during ischaemia/reperfusion and that protein kinase C modulates the effects of H2O2.
Tanaka
H
H
Department of Laboratory Medicine, Kyoto Prefectural University of Medicine, Karnigyo-ku, Kyoto 602-0841, Japan. hideotan@koto.kpu-m.ac.jp
Habuchi
Y
Y
Suto
F
F
Morikawa
J
J
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects*; D016877:Oxidants / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011817:Rabbits
D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D016877:Oxidants; D006861:Hydrogen Peroxide; D015761:4-Aminopyridine; D011493:Protein Kinase C; C088060:bisindolylmaleimide; D004229:Dithiothreitol