Monitoring mitochondrial electron fluxes using NAD(P)H-flavoprotein fluorometry reveals complex action of isoflurane on cardiomyocytes.

Biochimica Et Biophysica Acta
Filip SedlicMartin Bienengraeber

Abstract

Mitochondrial bioenergetic studies mostly rely on isolated mitochondria thus excluding the regulatory role of other cellular compartments important for the overall mitochondrial function. In intact cardiomyocytes, we followed the dynamics of electron fluxes along specific sites of the electron transport chain (ETC) by simultaneous detection of NAD(P)H and flavoprotein (FP) fluorescence intensities using a laser-scanning confocal microscope. This method was used to delineate the effects of isoflurane, a volatile anesthetic and cardioprotective agent, on the ETC. Comparison to the effects of well-characterized ETC inhibitors and uncoupling agent revealed two distinct effects of isoflurane: uncoupling-induced mitochondrial depolarization and inhibition of ETC at the level of complex I. In correlation, oxygen consumption measurements in cardiomyocytes confirmed a dose-dependent, dual effect of isoflurane, and in isolated mitochondria an obstruction of the ETC primarily at the level of complex I. These effects are likely responsible for the reported mild stimulation of mitochondrial reactive oxygen species (ROS) production required for the cardioprotective effects of isoflurane. In conclusion, isoflurane exhibits complex effects on ...Continue Reading

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Citations

Aug 21, 2013·Basic Research in Cardiology·Damien De PaulisMichel Ovize
Oct 18, 2014·British Journal of Pharmacology·C KikuchiM Bienengraeber
Jul 17, 2012·European Journal of Pharmacology·Danijel PravdicMartin Bienengraeber
Nov 10, 2011·Biophysical Journal·Natalja JepihhinaMarko Vendelin
Dec 21, 2013·Biochimica Et Biophysica Acta·Bhawana AgarwalAmadou K S Camara
Oct 4, 2014·Frontiers in Physiology·Bhawana AgarwalAmadou K S Camara
Dec 19, 2013·Anesthesiology·Maria MuravyevaJudy R Kersten
Mar 23, 2017·Journal of Cardiovascular Pharmacology·Rania HarissehAbdallah Gharib
Nov 2, 2016·Chemical Communications : Chem Comm·Dong-Nam LeeJong-In Hong

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