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.