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

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 H2 O2 on [Ca2+ ]i handling and contractility in the rat ventricular myocyte...

Full description

Saved in:
Bibliographic Details
Published in:Cell calcium (Edinburgh) 2010-12, Vol.48 (6), p.341-351
Main Authors: Greensmith, David J, Eisner, David A, Nirmalan, Mahesh
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Calcium
Calcium - metabolism
Calcium Channels, L-Type - metabolism
Cell Size
Hydrogen Peroxide - pharmacology
In Vitro Techniques
Male
Myocardial Contraction
Myocyte
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - physiology
Rats
Rats, Wistar
Reactive oxygen species
Reactive Oxygen Species - metabolism
Ryanodine Receptor Calcium Release Channel - metabolism
Sarcoplasmic reticulum
Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism
Sodium-Calcium Exchanger - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 H2 O2 on [Ca2+ ]i handling and contractility in the rat ventricular myocyte. This was achieved using patch clamping, [Ca2+ ]i measurement using Fluo-3, video edge detection and confocal microscopy. All experiments were performed at 37 °C. 200 μM H2 O2 resulted in a 44% decrease in the [Ca2+ ]i transient amplitude, a 30% increase in diastolic [Ca2+ ]i and an 18% decrease in the rate of systolic Ca2+ 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 [Ca2+ ]i transient amplitude could be explained by a 27% decrease in SR Ca2+ content. This, in turn results from a 22% decrease of SERCA activity. The decreased SR Ca2+ content also provides a mechanism for a reduction in [Ca2+ ]i spark frequency with no evidence for a Ca2+ independent modification of ryanodine receptor open probability. We conclude that decreased SERCA activity is the major factor responsible for the changes of the systolic [Ca2+ ]i transient.
ISSN:0143-4160
1532-1991
DOI:10.1016/j.ceca.2010.10.007