Abundance and subcellular distribution of MCT1 and MCT4 in heart and fast-twitch skeletal muscles

Bonen, Arend, Dragana Miskovic, Mio Tonouchi, Kathleen Lemieux, Mariengela C. Wilson, Andre Marette, and Andrew P. Halestrap. Abundance and subcellular distribution of MCT1 and MCT4 in heart and fast-twitch skeletal muscles. Am J Physiol Endocrinol Metab 278: E1067-E1077, 2000.--The expression of two monocarboxylate transporters (MCTs) was examined in muscle and heart. MCT1 and MCT4 proteins are coexpressed in rat skeletal muscles, but only MCT1 is expressed in rat hearts. Among six rat fast-twitch muscles (red and white gastrocnemius, plantaris, extensor digitorum longus, red and white tibialis anterior) there was an inverse relationship between MCT1 and MCT4 (r = -0.94). MCT1 protein was correlated with MCT1 mRNA (r = 0.94). There was no relationship between MCT4 mRNA and MCT4 protein. MCT1 (r = -0.97) and MCT4 (r = 0.88) protein contents were correlated with percent fast-twitch glycolytic fiber. When normalized for their mRNAs, MCT1 but not MCT4 was still correlated with the percent fast-twitch glycolytic fiber composition of rat muscles (r = -0.98). MCT1 and MCT4 were also measured in plasma membranes (PM), triads (TR), T tubules (TT), sarcoplasmic reticulum (SR), and intracellular membranes (IM). There was an intracellular pool of MCT4 but not of MCT1. The MCT1 subcellular distribution was as follows: PM (100%) [is greater than] TR (31.6%) [is greater than] SR (15%) = TT (14%) [is greater than] IM (1.7%). The MCT4 subcellular distribution was considerably different [PM (100%) [is greater than] TR (66.5%) [is greater than] TT (36%) = SR (43%) [is greater than] IM (24%)]. These studies have shown that 1) the mechanisms regulating the expression of MCT1 (transcriptional and posttranscriptional) and MCT4 (posttranscriptional) are different and 2) differences in MCT1 and MCT4 expression among muscles, as well as in their subcellular locations, suggest that they may have different roles in muscle. lactate; transport; transporters; fast-twitch fibers; plasma membrane; T tubules, messenger ribonucleic acid; monocarboxylate transporter 1; monocarboxylate transporter 4