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Effects of superoxide donor menadione in adult Rat myocardium are associated with increased diastolic intracellular calcium
Rogers, L.J. Lake, A.J. White, K. Hardy, Matthew E. White, E.
Rogers, L.J.
Lake, A.J.
White, K.
Hardy, Matthew E.
White, E.
Publication Date
2014-02-12
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© 2014 The Authors. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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2013-09-16
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Abstract
Superoxide anions have been associated with many aspects of cardiovascular disease. Menadione is a superoxide anion donor
that alters the heart’s electrical and mechanical functions. The aim of this study was to demonstrate simultaneous changes in
intracellular Ca2+ ([Ca2+]i) and mechanical activity in intact adult cardiac myocytes, and mechanical activity and electrical activity
in isolated whole hearts in order to provide greater insight into the mechanisms associated with the detrimental effects of
menadione on the myocardium. Isolated hearts from adult male Wistar rats (n = 11, 200–250 g) were Langendorff perfused at
38°C with a Krebs–Henseleit solution. A saline-filled balloon was placed in the left ventricle (LV) in order to measure diastolic
and developed pressure. Monophasic action potentials were simultaneously recorded from the epicardial surface. External
stimulation at 5 Hz and intrinsic pacing were used throughout a 10 min control period and 30 min exposure to 50 μM menadione.
Single LV myocytes (n = 7 from n = 4 animals) were loaded with the Ca2+-indicator Fura4-AM, stimulated at 1 Hz and
exposed to 50 μM menadione. Myocyte length was simultaneously measured with [Ca2+]i using a video edge detection system.
In isolated hearts, exposure to menadione significantly decreased contractility and action potential duration (with a similar
time course); intrinsic heart rate and rhythmicity. Diastolic pressure was significantly increased. In single adult myocytes,
menadione caused a significant increase in diastolic [Ca2+]i and a decrease in resting cell length and led to spontaneous release
of [Ca2+]i. We conclude that the effects of menadione upon electrical and mechanical activity of the heart are at least in part a
consequence of dysregulation of [Ca2+]i handling and the subsequent increase in diastolic [Ca2+] alterations in [Ca2+]i are
consistent with the generation of delayed after depolarization arrhythmias.
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Citation
Rodgers LJ, Lake AJ, White K, Hardy M and White E (2014) Effects of superoxide donor menadione in adult Rat myocardium are associated with increased diastolic intracellular calcium. Bioscience Horizons. 7 ( hzt012): 1-8.
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