Wu, Yuejin and Rasmussen, Tyler P. and Koval, Olha M. and Joiner, Mei-ling A. and Hall, Duane D. and Chen, Biyi and Luczak, Elizabeth D. and Wang, Qiongling and Rokita, Adam G. and Wehrens, Xander H. T. and Song, Long-Sheng and Anderson, Mark E. (2015) The mitochondrial uniporter controls fight or flight heart rate increases. NATURE COMMUNICATIONS, 6: 6081. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ESSENTIAL COMPONENT; PACEMAKER ACTIVITY; INTERNAL STORE; CA2+ RELEASE; KINASE-II; CALCIUM; PROTEIN; PHOSPHORYLATION; MECHANISM; CHANNELS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Aug 2019 08:55 |
| Last Modified: | 02 Aug 2019 08:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/6315 |
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