Greensmith, DJ, Eisner, DA and Nirmalan, M 2010, 'The effects of hydrogen peroxide on intracellular calcium handling and contractility in the rat ventricular myocyte' , Cell Calcium, 48 (6) , pp. 341-51.
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Elevations in reactive oxygen species are implicated in many disease states and cause systolic and diastolic myocardial dysfunction. To understand the underlying cellular dysfunction, we characterised the effects of H₂O₂ on [Ca(2+)](i) handling and contractility in the rat ventricular myocyte. This was achieved using patch clamping, [Ca(2+)](i) measurement using Fluo-3, video edge detection and confocal microscopy. All experiments were performed at 37°C. 200 μM H₂O₂ resulted in a 44% decrease in the [Ca(2+)](i) transient amplitude, a 30% increase in diastolic [Ca(2+)](i) and an 18% decrease in the rate of systolic Ca(2+) removal. This was associated with a 61% reduction in systolic shortening, a contracture of 3 μm and a 42% increase in relaxation time respectively. The decrease in the [Ca(2+)](i) transient amplitude could be explained by a 27% decrease in SR Ca(2+) content. This, in turn results from a 22% decrease of SERCA activity. The decreased SR Ca(2+) content also provides a mechanism for a reduction in [Ca(2+)](i) spark frequency with no evidence for a Ca(2+) independent modification of ryanodine receptor open probability. We conclude that decreased SERCA activity is the major factor responsible for the changes of the systolic [Ca(2+)](i) transient.
|Themes:||Health and Wellbeing
Subjects outside of the University Themes
|Schools:||Schools > School of Environment and Life Sciences|
|Journal or Publication Title:||Cell Calcium|
|Funders:||British Heart Foundation|
|Depositing User:||D Greensmith|
|Date Deposited:||26 Jan 2015 18:05|
|Last Modified:||05 Apr 2016 18:19|
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