The expression of lactate transporters (MCT1 and MCT4) in heart and muscle

Abstract.

It is now known that lactate traverses the plasma membrane of many tissues, including heart and muscle, via a stereo-specific, pH-dependent monocarboxylate transport (MCT) system. In the past few years a family of MCTs (MCT1–MCT7) has been cloned. Transcripts of MCT1 and MCT4 are detectable in rat and human skeletal muscle and in the heart. However, only skeletal muscle expresses both the MCT1 and MCT4 proteins, whereas rat heart expresses the MCT1, but not the MCT4 protein. The kinetic activities of MCT1(K _m=3.5 mM) and MCT4 (K _m=17–34 mM) are quite different. Among rat muscles, MCT1 expression is highly correlated with the oxidative fiber composition of the muscle, and other indices of oxidative metabolism. Lactate uptake from the circulation is also highly correlated with the MCT1 content of muscles. MCT4 is confined to fast-twitch (fast glycolytic and fast oxidative glycolytic) muscle fibers, in which MCT4 content is correlated with indices of anaerobic metabolism. Collectively, these data suggest that MCT1 and MCT4 are primarily responsible for lactate uptake from the circulation and lactate extrusion out of muscle, respectively. Exercise training can increase the expression of both MCT1 and MCT4 in human muscle, although the extent of this up-regulation may be related to the intensity of training. In the rat heart, MCT1 expression is induced more easily by exercise training than in rat skeletal muscle. It appears that MCT1 and MCT4 expression are regulated in a tissue-specific and isoform-specific manner. Therefore, skeletal muscle lactate concentrations are not only regulated by the rate of glycolysis, but also by the efficiency of trans-sarcolemmal lactate transport, a process that is regulated by the quantity of available MCT proteins.