Lactate transport in skeletal muscle - role and regulation of the monocarboxylate transporter

Skeletal muscle is the major producer of lactic acid in the body, but its o xidative fibres also use lactic acid as a respiratory fuel. The stereoselec tive transport of L-lactic acid across the plasma membrane of muscle fibres has been shown to involve a proton-linked monocarboxylate transporter (MCT ) similar to that described in erythrocytes and other cells. This transport er plays an important role in the pH regulation of skeletal muscle. A famil y of eight MCTs has now been cloned and sequenced, and the tissue distribut ion of each isoform varies. Skeletal muscle contains both MCT1 (the only is oform found in erythrocytes but also present in most other cells) and MCT4. The latter is found in all fibre types, although least in more oxidative r ed muscles such as soleus, whereas expression of MCT1 is highest in the mor e oxidative muscles and very low in white muscles that are almost entirely glycolytic. The properties of MCT1 and MCT2 have been described in some det ail and the latter shown to have a higher affinity for substrates. MCT4 has been less well characterized but has a lower affinity for L-lactate (i.e. a higher K-m, of 20 mM) than does MCT1 (K-m of 5 mM). MCT1 expression is in creased in response to chronic stimulation and either endurance or explosiv e exercise training in rats and humans, whereas denervation decreases expre ssion of both MCT1 and MCT4. The mechanism of regulation is not established , but does not appear to be accompanied by changes in mRNA concentrations. However, in other cells MCT1 and MCT4 are intimately associated with an anc illary protein OX-47 (also known as CD147). This protein is a member of the immunoglobulin superfamily with a single transmembrane helix, whose expres sion is known to be increased in a range of cells when their metabolic acti vity is increased.