Lactate/proton co-transport in skeletal muscle: regulation and importance for pH homeostasis

In skeletal muscle, intracellular pH is more alkaline than would be predicted if H+ were passively distributed across the sarcolemma. Therefore, the passive influx of H+ must be counteracted by transport processes mediating H+ afflux. In resting skeletal muscle, these transport processes are Na+/H+ exchange and bicarbonate-dependent systems. During periods of high energy demand, skeletal muscle produces large amounts of lactic acid. The internal accumulation of lactic acid reduces pH, which may cause fatigue. It is therefore important for muscle cells to be able to regulate pH during and after activity. A part of the accumulated lactate and H+ is metabolized, but a considerable fraction is released from the cell. The efflux of H+ and lactate might be mediated by the lactate/proton co-transport system found in almost all cell types in the body. The role of lactate/proton co-transport in pH regulation has been studied both with intact cells and with sarcolemmal vesicles. In intact cells, inhibitors of lactate/proton transport have been shown to accelerate the development of fatigue, and to delay the recovery after activity. A comparison with vesicles has demonstrated that, at low pH, and with a high lactate concentration, the capacity for H+ removal is higher via the lactate/proton co-transport system than via the sum of the Na+/H+ exchange and bicarbonate-dependent exchange systems. Therefore, the carrier-mediated lactate/proton efflux is of major importance for pH regulation in connection with muscle activity. The lactate/proton transport system has been shown to undergo long-term changes depending on the level of physical activity. The capacity of the system was enhanced after intense training or chronic stimulation, and reduced after denervation. It is concluded that the lactate/proton transport system is of major importance for pH regulation in skeletal muscle, and that changes in the amount of transporters are one of the many adaptations to physical activity.