New Insights into the Lactate Shuttle: Role of MCT4 in the Modulation of the Exercise Capacity
27 Pages Posted: 26 Jul 2019 Sneak Peek Status: PublishedMore...
Lactate produced by muscle during high intensity activity is an important glycolytic intermediate that supports whole body metabolism. The lactate shuttle model suggest that lactate produced by glycolytic cells is utilized by oxidative ones. MCT4 controls the efflux of lactate from glycolytic muscles. 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-/-). While MCT4-/- and iMSBsg-/- mice have normal muscle morphology and contractility, only MCT4-/- mice exibit a progressive exercise intolerance. In vivo measurements of compound muscle action potentials showed a decrement in the amplitude of the evoked response in the MCT4-/- mice. This reflected in a significant structural degeneration of the neuromuscular junctions (NMJs). We propose that the disruption of the lactate shuttle impacts motor function by destabilizing the motor unit at the level of the NMJ.
Keywords: lactate, MCT4, Exercise, muscle, NMJ, fatigue, Monocarboxylate transporters, lactate shuttle
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