The effects of hydrogen peroxide on intracellular calcium handling and contractility in the rat ventricular myocyte

Greensmith, DJ; Eisner, DA; Nirmalan, M

Abstract

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.

Citation

Greensmith, D., Eisner, D., & Nirmalan, M. (2010). The effects of hydrogen peroxide on intracellular calcium handling and contractility in the rat ventricular myocyte. Cell Calcium, 48(6), 341-51. https://doi.org/10.1016/j.ceca.2010.10.007

• Journal Article Type: Article
• Publication Date: Dec 1, 2010
• Deposit Date: Jan 26, 2015
• Journal: Cell Calcium
• Print ISSN: 0143-4160
• Electronic ISSN: 0143-4160
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 48
• Issue: 6
• Pages: 341-51
• DOI: https://doi.org/10.1016/j.ceca.2010.10.007
• Publisher URL: http://dx.doi.org/10.1016/j.ceca.2010.10.007
• Related Public URLs: http://www.journals.elsevier.com/cell-calcium/