Electrophysiologic alterations in the rabbit nodal cells induced by membrane lipid peroxidation.
To investigate cellular electrophysiologic alterations due to lipid peroxidation of the cell membrane by free radicals as a possible cause of coronary reperfusion arrhythmias, we studied the effects of t-butyl hydroperoxide on the spontaneous action potential and membrane currents of the rabbit sinoatrial and atrioventricular node preparations (0.2 x 0.2 x 0.1 mm). 1-5 min of superfusion with t-butyl hydroperoxide (100-500 microM) caused a transient increase in the spontaneous firing frequency by 9%, accompanied by a 4% increase in the action potential amplitude and a 33% increase in the maximal rate of depolarization (P < 0.05, n = 6). t-Butyl hydroperoxide then gradually suppressed physiological automaticity, but induced abnormal repetitive firing due to early and delayed after-depolarizations. 15 min of superfusion with t-butyl hydroperoxide caused a complete standstill of nodal cells at a resting potential of -46 +/- 3 mV (n = 12). Such effects of t-butyl hydroperoxide on the spontaneous action potential were attenuated by pretreating the cells with butylated hydroxytoluene, a lipid peroxidation inhibitor. Voltage clamp experiments using double microelectrode methods revealed that t-butyl hydroperoxide transiently increased the Ca2+ current by 22% after 5 min of superfusion but subsequently reduced it to 46% of the control value after 15 min (P < 0.05, n = 6). Similar biphasic changes were observed in the delayed rectifying K+ current and hyperpolarization-activated inward current (n = 6). Background current was progressively increased without any change in its reversal potential (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)
Satoh
N
N
Cardiovascular Institute, Fujita Health University School of Medicine, Aichi, Japan.
Nishimura
M
M
Watanabe
Y
Y
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001283:Atrioventricular Node / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008563:Membrane Lipids / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010545:Peroxides / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020122:tert-Butylhydroperoxide
D015220:Calcium Channels; D007473:Ion Channels; D008563:Membrane Lipids; D010545:Peroxides; D015221:Potassium Channels; D020122:tert-Butylhydroperoxide