In-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler
We recently reported a method using positron emission tomography (PET) and the tracer F-labeled tetraphenylphosphonium ( F-TPP ) for mapping the tissue (i.e., cellular plus mitochondrial) membrane potential (ΔΨ ) in the myocardium. The purpose of this work is to provide additional experimental evide...
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Published in | Frontiers in physiology Vol. 11; p. 491 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
15.05.2020
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Subjects | |
Online Access | Get full text |
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Summary: | We recently reported a method using positron emission tomography (PET) and the tracer
F-labeled tetraphenylphosphonium (
F-TPP
) for mapping the tissue (i.e., cellular plus mitochondrial) membrane potential (ΔΨ
) in the myocardium. The purpose of this work is to provide additional experimental evidence that our methods can be used to observe transient changes in the volume of distribution for
F-TPP
and mitochondrial membrane potential (ΔΨ
).
We tested these hypotheses by measuring decreases of
F-TPP
concentration elicited when a proton gradient uncoupler, BAM15, is administered by intracoronary infusion during PET scanning. BAM15 is the first proton gradient uncoupler shown to affect the mitochondrial membrane without affecting the cellular membrane potential. Preliminary dose response experiments were conducted in two pigs to determine the concentration of BAM15 infusate necessary to perturb the
F-TPP
concentration. More definitive experiments were performed in two additional pigs, in which we administered an intravenous bolus plus infusion of
F-TPP
to reach secular equilibrium followed by an intracoronary infusion of BAM15.
Intracoronary BAM15 infusion led to a clear decrease in
F-TPP
concentration, falling to a lower level, and then recovering. A second BAM15 infusion reduced the
F-TPP
level in a similar fashion. We observed a maximum depolarization of 10 mV as a result of the BAM15 infusion.
This work provides evidence that the total membrane potential measured with
F-TPP
PET is sensitive to temporal changes in mitochondrial membrane potential. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Zhen Cheng, Stanford University, United States Reviewed by: Mike MingQiang Zheng, Yale University School of Medicine, United States; Lina Wu, Harbin Medical University, China This article was submitted to Medical Physics and Imaging, a section of the journal Frontiers in Physiology These authors share first authorship |
ISSN: | 1664-042X 1664-042X |
DOI: | 10.3389/fphys.2020.00491 |