Document Type

Article

Publication Date

11-26-2019

Comments

This article has been peer-reviewed. It is the author's final published version in iScience, Volume 22, November 2019, Pages 507-518

The published version is available at https://doi.org/10.1016/j.isci.2019.11.041. Copyright © Bisetto et.al.

Abstract

Lactate produced by muscle during high-intensity activity is an important end product of glycolysis that supports whole body metabolism. The lactate shuttle model suggested that lactate produced by glycolytic muscle fibers is utilized by oxidative fibers. MCT4 is a proton coupled monocarboxylate transporter preferentially expressed in glycolytic muscle fibers and facilitates the lactate efflux. Here we investigated the exercise capacity of mice with disrupted lactate shuttle due to global deletion of MCT4 (MCT4−/−) or muscle-specific deletion of the accessory protein Basigin (iMSBsg−/−). Although MCT4−/− and iMSBsg−/− mice have normal muscle morphology and contractility, only MCT4−/− mice exhibit an exercise intolerant phenotype. In vivo measurements of compound muscle action potentials showed a decrement in the evoked response in the MCT4−/− mice. This was accompanied by a significant structural degeneration of the neuromuscular junctions (NMJs). We propose that disruption of the lactate shuttle impacts motor function and destabilizes the motor unit.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-No Derivative Works 4.0 License.

PubMed ID

31837519

Language

English

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