Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: In vivo insights from MCT1 haploinsufficient mice

Abstract

The purpose of this study was to investigate the effects of a partial suppression of monocarboxylate transporter (MCT)-1 on skeletalmuscle pH, energetics, and function (MCT1+/- mice). Twenty-four MCT1+/- and 13 wild-type (WT) mice were subjected to a rest-exercise-recovery protocol, allowing assessment ofmuscle energetics (bymagnetic resonance spectroscopy) and function. The study included analysis of enzyme activities and content of protein involved in pH regulation. Skeletalmuscle of MCT1+/-micehad lower MCT1 (-61%;P< 0.05) and carbonic anhydrase (CA)-II (-54%; P < 0.05) contents. Although intramuscular pH was higher in MCT1+/- mice at rest (P < 0.001), the mice showed higher acidosis during the first minute of exercise (P < 0.01). Then, the pH time course was similar among groups until exercise completion.MCT1+/- mice had higher specific peak (P < 0.05) and maximumtetanic (P< 0.01) forces and lower fatigability (P< 0.001) when compared to WT mice. Weconclude that both MCT1 and CAII are involved in the homeostatic control of pH in skeletal muscle, both at rest and at the onset of exercise. The improved muscle function and resistance to fatigue in MCT1+/- mice remain unexplained.