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 (INa) in isolated feline ventricular myocytes were studied using whole-cell patch clamp techniques under 100% O2 bubbling. This agent at 20 mM inhibited INa from 2.2 +/- 1.3 to 1.7 +/- 1.0 nA (P < 0.01, n = 7) without changing time courses of INa inactivation. Twenty millimoles TBH shifted the steady-state inactivation curve for INa from -77.4 +/- 1.7 to -81.3 +/- 1.8 mV when measured at INa half inhibition voltage (P < 0.01, n = 7), but did not affect the slope factor. The kinetics of INa recovery from inactivation remained unchanged. These findings suggest that lipid peroxidation in the membrane by TBH reduces INa conductance and voltage-dependent INa availability, most likely as a result of structural damage to the Na+ channels.
Uchida
T
T
First Department of Medicine, Nippon Medical School, Tokyo, Japan.
Nishimura
M
M
Saeki
T
T
Watanabe
Y
Y
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology; D002415:Cats; D002478:Cells, Cultured; D006352:Heart Ventricles; D015227:Lipid Peroxidation / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000503:physiopathology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010545:Peroxides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D020122:tert-Butylhydroperoxide
D010545:Peroxides; D017382:Reactive Oxygen Species; D015222:Sodium Channels; D020122:tert-Butylhydroperoxide