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.