Lactic acidosis, a typical response to strenuous muscular exercise, is important because of the metabolic role of lactic acid and its effect on the performance of cardiac and skeletal muscle. Blood lactate concentration is a balance between production and utilization. Skeletal muscle has usually been viewed as a producer of lactate. However, it is known that skeletal muscle can take up lactate, particularly when blood lactate concentration is elevated. The major goal of this proposal is to determine the regulators of lactate uptake by skeletal muscle. In situ dog an, cat gastrocnemius-plantaris (GTN) muscle preparations will be utilized to answer several questions. 1) What are the effects of metabolic rate and blood lactate concentration on lactate uptake by skeletal muscle? The dog GTN will be stimulated to contract at different frequencies, resulting in different metabolic rates. At each metabolic rate, lactate will be infused into the muscle's arterial inflow to establish concentrations of 10, 25, 50, and 100 mM. These experiments will permit determination of the saturation of steady state lactate uptake at different metabolic rates which should provide different rates of lactate utilization. 2) Does lactate uptake differ in muscles composed of different fiber types? Meta- bolic characteristics and enzyme profiles (especially lactic dehydrogenase and malate-aspartate shuttle enzymes) suggest that slow twitch, oxidative fibers are more likely to take up and utilize lactate than are fast twitch, glycolytic fibers. The experiments described for the dog GTN will be performed on the cat GTN, thus providing a direct comparison of steady state lactate uptake by muscles of divergent oxidative capacity. Succinate oxidase activity in the dog GTN is three times greater than that of the cat GTN. 3) Does a membrane transport system determine lactate uptake by skeletal muscle? A dual tracer technique will be used to measure unidirectional lactate influx to determine membrane characteristics at rest and during contractions. The effect of known blockers of lactate carriers on steady state lactate uptake and unidirectional lactate influx will also be determined.
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