Ionic mechanism of the effects of hydrogen peroxide in rat ventricular myocytes.

Ward, Christopher A.; Giles, Wayne R.

doi:10.1113/jphysiol.1997.sp022048

Cited by 184 publications

(168 citation statements)

References 41 publications

(51 reference statements)

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“…Although previous studies have observed a persistent inward Na ϩ current during oxidative stress 25 and exposure to hydrogen peroxide (H 2 O 2 ), 26 we did not observe a noninactivating component during exposure to t-BHP or IsoK. This could be attributable to differences in mechanism of action (t-BHP and IsoK, but not H 2 O 2 , are localized in the membrane) or species differences.…”

Section: Channel Availabilitycontrasting

confidence: 53%

Oxidative Mediated Lipid Peroxidation Recapitulates Proarrhythmic Effects on Cardiac Sodium Channels

Fukuda

Davies

Nakajima

et al. 2005

Circulation Research

118

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Abstract-Sudden cardiac death attributable to ventricular tachycardia/fibrillation (VF) remains a catastrophic outcome of myocardial ischemia and infarction. At the same time, conventional antagonist drugs targeting ion channels have yielded poor survival benefits. Although pharmacological and genetic models suggest an association between sodium (Na ϩ ) channel loss-of-function and sudden cardiac death, molecular mechanisms have not been identified that convincingly link ischemia to Na ϩ channel dysfunction and ventricular arrhythmias. Because ischemia can evoke the generation of reactive oxygen species, we explored the effect of oxidative stress on Na ϩ channel function. We show here that oxidative stress reduces Na ϩ channel availability. Both the general oxidant tert-butyl-hydroperoxide and a specific, highly reactive product of the isoprostane pathway of lipid peroxidation, E 2 -isoketal, potentiate inactivation of cardiac Na ϩ channels in human embryonic kidney (HEK)-293 cells and cultured atrial (HL-1) myocytes. Furthermore, E 2 -isoketals were generated in the epicardial border zone of the canine healing infarct, an arrhythmogenic focus where Na ϩ channels exhibit similar inactivation defects. In addition, we show synergistic functional effects of flecainide, a proarrhythmic Na ϩ channel blocker, and oxidative stress. These data suggest Na ϩ channel dysfunction evoked by lipid peroxidation is a candidate mechanism for ischemia-related conduction abnormalities and arrhythmias.

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Section: Channel Availabilitycontrasting

confidence: 53%

Oxidative Mediated Lipid Peroxidation Recapitulates Proarrhythmic Effects on Cardiac Sodium Channels

Fukuda

Davies

Nakajima

et al. 2005

Circulation Research

118

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“…Here, we show in computational simulations and supporting evidence from experiments of isolated myocytes that this irregularity is dynamical chaos, i.e., irregular dynamics from a deterministic system. EADs were induced in patch-clamped isolated rabbit cardiac myocytes by exposure to 1 mM H 2 O 2 , which promotes EADs by enhancing inward currents during repolarization, including the late Na ϩ current and the L-type Ca 2ϩ current (13,25,26). At different pacing cycle lengths (PCLs), we observed different EAD pat-terns with 1 example shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Synchronization of chaotic early afterdepolarizations in the genesis of cardiac arrhythmias

Sato¹,

Xie²,

Sovari³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

236

300

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The synchronization of coupled oscillators plays an important role in many biological systems, including the heart. In heart diseases, cardiac myocytes can exhibit abnormal electrical oscillations, such as early afterdepolarizations (EADs), which are associated with lethal arrhythmias. A key unanswered question is how cellular EADs partially synchronize in tissue, as is required for them to propagate. Here, we present evidence, from computational simulations and experiments in isolated myocytes, that irregular EAD behavior is dynamical chaos. We then show in electrically homogeneous tissue models that chaotic EADs synchronize globally when the tissue is smaller than a critical size. However, when the tissue exceeds the critical size, electrotonic coupling can no longer globally synchronize EADs, resulting in regions of partial synchronization that shift in time and space. These regional partially synchronized EADs then form premature ventricular complexes that propagate into recovered tissue without EADs. This process creates multiple hat propagate “shifting” foci resembling polymorphic ventricular tachycardia. Shifting foci encountering shifting repolarization gradients can also develop localized wave breaks leading to reentry and fibrillation. As predicted by the theory, rabbit hearts exposed to oxidative stress (H 2 O 2 ) exhibited multiple shifting foci causing polymorphic tachycardia and fibrillation. This mechanism explains how collective cellular behavior integrates at the tissue scale to generate lethal cardiac arrhythmias over a wide range of heart rates.

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“…However in literature the data concerning the effect of ROS on potassium current are controversal. For example, Cerbai et al (1991) and Ward & Giles (1997) did not observe any effect, in contrast to Tarr & Valenzeno (1989) who obtained a decrease in the outward, delayed rectifier potassium current. The results of Hasan et al (2007) suggest that oxidative stress, which inhibits the delayed-rectifier current, can alter neural activity.…”

Section: Wwwintechopencommentioning

confidence: 92%

Effects of Oxidative Stress on the Electrophysiological Function of Neuronal Membranes

Jovanović¹

2012

Oxidative Stress and Diseases

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Ionic mechanism of the effects of hydrogen peroxide in rat ventricular myocytes.

Cited by 184 publications

References 41 publications

Oxidative Mediated Lipid Peroxidation Recapitulates Proarrhythmic Effects on Cardiac Sodium Channels

Oxidative Mediated Lipid Peroxidation Recapitulates Proarrhythmic Effects on Cardiac Sodium Channels

Synchronization of chaotic early afterdepolarizations in the genesis of cardiac arrhythmias

Effects of Oxidative Stress on the Electrophysiological Function of Neuronal Membranes

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