EFFECTS OF MEMBRANE LIPID-PEROXIDATION BY TERT-BUTYL HYDROPEROXIDE ON THE SODIUM CURRENT IN ISOLATED FELINE VENTRICULAR MYOCYTES

Membrane lipid peroxidation is known to play a pivotal role in the genesis of coronary reperfusion arrhythmias in both experimental and clinical settings. To elucidate the electrophysiological mechanisms underlying these arrhythmias, the effects of tert butyl hydroperoxide (TBH) on the Na+ current (I(Na)) in isolated feline ventricular myocytes were studied using whole-cell patch clamp techniques under 100% O2 bubbling. This agent at 20 mM inhibited I(Na) from 2.2 +/- 1.3 to 1.7 +/- 1.0 nA (P < 0.01, n = 7) without changing time courses of I(Na) inactivation. Twenty millimoles TBH shifted the steady-state inactivation curve for I(Na) from -77.4 +/- 1.7 to -81.3 +/- 1.8 mV when measured at I(Na) half inhibition voltage (P < 0.01, n = 7), but did not affect the slope factor. The kinetics of I(Na) recovery from inactivation remained unchanged. These findings suggest that lipid peroxidation in the membrane by TBH reduces I(Na) conductance and voltage-dependent I(Na) availability, most likely as a result of structural damage to the Na+ channels.