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

Aim: To study the effect of hydrogen peroxide (H2O2) on persistent sodium current (I-Na,I-P) in guinea pig ventricular myocytes. Methods: The whole-cell, cell-attached, and inside-out patch-clamp techniques were applied on isolated ventricular myocytes from guinea pig. Results: H2O2 (0.1 mmol/L 0.5 mmol/L and 1.0 mmol/L) increased the amplitude of whole-cell I-NaP in a concentration-dependent manner, and glutathione (GSH 1 mmol/L) reversed the increased I-Na,I-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 (P< 0.01 vs control). They were then decreased to 0.039 +/- 0.024 and 0.027 +/- 0.006, respectively, after the addition of I mmol/L GSH (P<0.01 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, P<0.01; 9.6 +/- 1.6 min vs 18.7 +/- 4.7 min, P<0.01). Conclusion: H2O2 increased the I-Na,I-P of guinea pig ventricular myocytes in a concentration-dependent manner, possibly by directly oxidating the cell membrane.