LACTATE TRANSPORT IN HEART IN RELATION TO MYOCARDIAL-ISCHEMIA

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 a re presented. These are monocarboxyl ate/proton symporters with a broad substrate specificity that includes L-lactate, pyruvate, and the ketone bodies acetate, acetoacetate, and beta-hydroxybutyrate. Although it is unlikely that lactic acid transp ort constrains heart metabolism under most conditions, it may do so du ring severe hypoxia or ischemia. The transporter plays a critical role in maintaining intracellular pH because it removes the protons that a re produced stoichiometrically with lactate during glycolysis. The kin etics and substrate and inhibitor specificities of the transport proce ss have been determined in cell suspensions using a radiotracer techni que and in single cells using a fluorescent measurement of the decreas e 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 MCT 1 and MCT2. Immunofluorescence microscopy shows that MCT1 expression i s restricted to the intercalated disk region, yet the rate of lactate transport in this region is slower than in the center of the cell, whe re there is no MCT1. New cDNA sequences with strong homology to MCT1 h ave been found in human cDNA libraries and Northern blots show that th e corresponding mRNA is expressed in rat heart. Expressions of these n ew MCT isoforms have yet to be demonstrated and their properties and c ellular distribution defined. (C) 1997 by Excerpta Medico, Inc.