Journal article
The mitochondrial uniporter controls fight or flight heart rate increases
Nature communications, Vol.6(1), pp.6081-6081
01/20/2015
DOI: 10.1038/ncomms7081
PMCID: PMC4398998
PMID: 25603276
Abstract
Heart rate increases are a fundamental adaptation to physiological stress, while inappropriate heart rate increases are resistant to current therapies. However, the metabolic mechanisms driving heart rate acceleration in cardiac pacemaker cells remain incompletely understood. The mitochondrial calcium uniporter (MCU) facilitates calcium entry into the mitochondrial matrix to stimulate metabolism. We developed mice with myocardial MCU inhibition by transgenic expression of a dominant-negative (DN) MCU. Here, we show that DN-MCU mice had normal resting heart rates but were incapable of physiological fight or flight heart rate acceleration. We found that MCU function was essential for rapidly increasing mitochondrial calcium in pacemaker cells and that MCU-enhanced oxidative phoshorylation was required to accelerate reloading of an intracellular calcium compartment before each heartbeat. Our findings show that MCU is necessary for complete physiological heart rate acceleration and suggest that MCU inhibition could reduce inappropriate heart rate increases without affecting resting heart rate.
Details
- Title: Subtitle
- The mitochondrial uniporter controls fight or flight heart rate increases
- Creators
- Yuejin Wu - Roy J. and Lucille A. Carver College of MedicineTyler P Rasmussen - University of IowaOlha M Koval - University of IowaMei-Ling A Joiner - University of IowaDuane D Hall - University of IowaBiyi Chen - University of IowaElizabeth D Luczak - Roy J. and Lucille A. Carver College of MedicineQiongling Wang - Baylor College of MedicineAdam G Rokita - Roy J. and Lucille A. Carver College of MedicineXander H T Wehrens - Baylor College of MedicineLong-Sheng Song - University of IowaMark E Anderson - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.6(1), pp.6081-6081
- DOI
- 10.1038/ncomms7081
- PMID
- 25603276
- PMCID
- PMC4398998
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Grant note
- R01-HL113001 / NHLBI NIH HHS R01 HL113001 / NHLBI NIH HHS R01 HL079031 / NHLBI NIH HHS R01 HL070250 / NHLBI NIH HHS R01-HL070250 / NHLBI NIH HHS R01-HL096652 / NHLBI NIH HHS R01 HL117641 / NHLBI NIH HHS R01-HL117641 / NHLBI NIH HHS F30-HL114258 / NHLBI NIH HHS R01 HL089598 / NHLBI NIH HHS R01-HL089598 / NHLBI NIH HHS F30 HL114258 / NHLBI NIH HHS R01 HL096652 / NHLBI NIH HHS R01 HL090905 / NHLBI NIH HHS R01-HL079031 / NHLBI NIH HHS
- Language
- English
- Date published
- 01/20/2015
- Academic Unit
- Cardiovascular Medicine; Biology; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984293091102771
Metrics
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