Muscle contraction increases lactate transport while reducing sarcolemmal MCT4, but not MCT1

Abstract

Rates of lactate uptake into giant sarcolemmal vesicles were determined in vesicles collected from rat muscles at rest and immediately after 10 min of intense muscle contraction. This contraction period reduced muscle glycogen rapidly by 37-82% in all muscles examined (P < 0.05) except the soleus muscle (no change P > 0.05). At an external lactate concentration of 1 mM lactate, uptake into giant sarcolemmal vesicles was not altered (P > 0.05), whereas at an external lactate concentration of 20 mM, the rate of lactate uptake was increased by 64% (P < 0.05). Concomitantly, the plasma membrane content of monocarboxylate transporter (MCT)1 was reduced slightly (-10%, P < 0.05), and the plasma membrane content of MCT4 was reduced further (-25%, P < 0.05). In additional studies, the 10-min contraction period increased the plasma membrane GLUT4 (P < 0.05) while again reducing MCT4 (-20%, P < 0.05) but not MCT1 (P > 0.05). These studies have shown that intense muscle contraction can increase the initial rates of lactate uptake, but only when the external lactate concentrations are high (20 mM). We speculate that muscle contraction increases the intrinsic activity of the plasma membrane MCTs, because the increase in lactate uptake occurred while plasma membrane MCT4 was decreased and plasma membrane MCT1 was reduced only minimally, or not at all.

Relationship between skeletal muscle MCT1 and accumulated exercise during voluntary wheel running

“…For the analysis of MCT, proteins were isolated from muscles as our laboratory has described previously (4,5,16,36,47,48). MCTs were detected with Western blotting.…”

“…Antibodies for MCT1 and MCT4 were raised in rabbits against the oligopeptide corresponding to the COOH terminus regions of each MCT (Qiagen, Tokyo, Japan). The procedures for the detection of MCT1 and MCT4 have been described in detail by our laboratory previously (4,5,16,36,47,48). MCT1 and MCT4 blots were quantified using a scanner (model GT-8700, Epson, Tokyo, Japan) with appropriate software (NIH Image 1.62, National Institutes of Health, Bethesda, MD).…”

“…It is now confirmed that there is a family of eight or more MCTs (21). MCT isoforms are expressed in a tissue-specific manner (2, 5, 15-18, 20, 26, 28, 36, 38 -40, 42, 47, 49), and MCTs are also coexpressed within the same tissue (2,4,5,16,29,42,47,49). These latter observations suggest that MCTs may have different roles and/or transport capacities.…”

“…Glycolytic muscle fibers express considerable quantities of MCT4, whereas MCT1 is predominantly present in oxidative muscle fibers in both slow-and fast-twitch muscles (2,5,12,16,36,42,47). It has been suggested that this MCT distribution among different types of muscle fibers may indicate that MCT1 is primarily involved with taking lactate up into the myocyte, whereas MCT4 may be primarily involved with extruding lactate (2,5,33).…”

T3increases lactate transport and the expression of MCT4, but not MCT1, in rat skeletal muscle

“…We also examined lactate uptake by giant sarcolemmal vesicles from control and 7-day-T3-treated animals. For these purposes, RG and WG muscles were pooled, and giant sarcolemmal vesicles were obtained as we have previously described (7,6,50). Briefly, muscles were scissored lengthwise into thin slices and incubated in 140 mM KCl, 5 mM MOPS, pH 7.4, 150 U/ml collagenase (type VII, Sigma), and 0.01 mg/ml protease inhibitor aprotinin (A1153, Sigma-Aldrich, St. Louis, MO) for 1 h at 34°C.…”