Lactate Transport in Heart in Relation to Myocardial Ischemia

Abstract

In this article, the importance of lactic acid transport into and out of heart cells is described and the properties of the monocarboxylate transporters (MCTs) responsible are presented. These are monocarboxylate/proton symporters with a broad substrate specificity that includes l-lactate, pyruvate, and the ketone bodies acetate, acetoacetate, and β-hydroxybutyrate. Although it is unlikely that lactic acid transport constrains heart metabolism under most conditions, it may do so during severe hypoxia or ischemia. The transporter plays a critical role in maintaining intracellular pH because it removes the protons that are produced stoichiometrically with lactate during glycolysis. The kinetics and substrate and inhibitor specificities of the transport process have been determined in cell suspensions using a radiotracer technique and in single cells using a fluorescent measurement of the decrease in intracellular pH that accompanies transport. The results of these experiments suggest the presence of 2 different transporter isoforms in heart cells, at least one of which is different from the cloned MCT1 and MCT2. Immunofluorescence microscopy shows that MCT1 expression is restricted to the intercalated disk region, yet the rate of lactate transport in this region is slower than in the center of the cell, where there is no MCT1. New cDNA sequences with strong homology to MCT1 have been found in human cDNA libraries and Northern blots show that the corresponding mRNA is expressed in rat heart. Expressions of these new MCT isoforms have yet to be demonstrated and their properties and cellular distribution defined.