Effect of hydrogen peroxide on persistent sodium current in guinea pig ventricular myocytes

To study the effect of hydrogen peroxide (H2O2) on persistent sodium current (I(Na.P)) in guinea pig ventricular myocytes.The whole-cell, cell-attached, and inside-out patch-clamp techniques were applied on isolated ventricular myocytes from guinea pig.H2O2 (0.1 mmol/L, 0.5 mmol/L and 1.0 mmol/L) increased the amplitude of whole-cell I(Na.P) in a concentration-dependent manner, and glutathione (GSH 1 mmol/L) reversed the increased I(Na.P). H2O2 (1 mmol/L) increased persistent sodium channel activity in cell-attached and inside-out patches. The mean open probability was increased from control values of 0.015+/-0.004 and 0.012+/-0.003 to 0.106+/-0.011 and 0.136+/-0.010, respectively (P0.01 vs control). They were then decreased to 0.039+/-0.024 and 0.027+/-0.006, respectively, after the addition of 1 mmol/L GSH (P0.01 vs H2O2). The time when open probability began to increase and reached a maximum was shorter in inside-out patches than that in cell-attached patches (4.8+/-1.0 min vs 11.5+/-3.9 min, P0.01; 9.6+/-1.6 min vs 18.7+/-4.7 min, P0.01).H2O2 increased the I(Na.P) of guinea pig ventricular myocytes in a concentration-dependent manner, possibly by directly oxidating the cell membrane.