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Hydrogen peroxide induced changes in membrane potentials in guinea pig ventricular muscle: permissive role of iron
1Department of Clinical Physiology, Medical Centre of Postgraduate Education, Warsaw, Poland.
Study Objective:
It has been proposed that oxygen free radicals trigger reperfusion arrhythmias. The mechanism of these arrhythmias is not clear. Thus, the effect of H2O2 on cellular action potentials was examined.
Design:
Trabecular muscles were superfused either with H2O2 alone or with H2O2 in combination either with H2O2 alone or with H2O2 in combination with iron ions or an iron chelating agent or various scavengers of oxygen free radicals. The effect of reduction of the superfusate calcium from 1.8 to 0.2 mmol.litre-1 on H2O2 induced changes was also studied.
Experimental Material:
Thin trabecular muscles isolated from the hearts of guinea pigs (200-300 g) of either sex were used.
Measurements And Main Results:
H2O2 (0.6 mmol.litre-1) caused a reproducible sequence of changes consisting of an initial increase in plateau height and in action potential duration, followed after 12-14 min by rapid action potential shortening accompanied by resting membrane depolarisation, reduction in action potential amplitude and dV/dt max, and by occasional appearance of late afterdepolarisations, leading finally to loss of excitability. This sequence of changes was: (1) accelerated by higher concentrations of H2O2, FeCl3 (0.1 mmol.litre-1), and FeCl2 (0.1 mmol.litre-1); (2) prevented by dimethylthiourea (10 mmol.litre-1) and desferrioxamine (2 mmol.litre-1); (3) not influenced by superoxide dismutase (150 units.ml-1), mannitol (5-50 mmol.litre-1) or PBN (50 mumols.litre-1); and (4) not prevented by a reduction of the superfusate calcium.
Conclusions:
The electrophysiological alterations induced by H2O2 are caused by a hydroxyl radical formed intracellularly in the iron catalysed Fenton reaction.
Insights
Hydrogen peroxide (H2O2) triggers cellular action potential changes, leading to arrhythmias. These effects are mediated by hydroxyl radicals formed via an iron-catalyzed Fenton reaction.
Area of Science:
- Cardiovascular Physiology
- Cellular Electrophysiology
- Free Radical Biology
Background:
- Oxygen free radicals are implicated in triggering reperfusion arrhythmias.
- The precise mechanism underlying these arrhythmias remains unclear.
Purpose of the Study:
- To investigate the effects of hydrogen peroxide (H2O2) on cellular action potentials.
- To elucidate the role of free radicals in H2O2-induced electrophysiological alterations.
Main Methods:
- Guinea pig cardiac trabecular muscles were superfused with H2O2, iron ions, chelating agents, or radical scavengers.
- Changes in action potential parameters were recorded.
- The influence of reduced extracellular calcium was also assessed.
Main Results:
- H2O2 induced a sequence of changes including action potential prolongation, followed by shortening, depolarization, and loss of excitability.
- These effects were accelerated by iron ions and inhibited by dimethylthiourea and desferrioxamine.
- Superoxide dismutase, mannitol, PBN, and reduced calcium did not prevent the H2O2-induced alterations.
Conclusions:
- Electrophysiological alterations induced by H2O2 are attributed to intracellular hydroxyl radical formation.
- The Fenton reaction, catalyzed by iron, is the mechanism responsible for hydroxyl radical generation.