Upregulation of the cardiac monocarboxylate transporter MCT1 in a rat model of congestive heart failure.
BACKGROUND
Cardiac metabolism becomes more dependent on carbohydrates in congestive heart failure (CHF), and lactate may be used as an important respiratory substrate. Monocarboxylate transporter 1 (MCT1) promotes cotransport of lactate and protons into and out of heart cells and conceivably flux of lactate between cells, because it is abundantly present in the intercalated disk.


RESULTS
Six weeks after induction of myocardial infarction (MI) in Wistar rats, left ventricular end-diastolic pressures were >15 mm Hg, signifying CHF. MCT1 and connexin43 protein levels in CHF were 260% and 20%, respectively, of those in sham-operated animals (Sham), and the corresponding mRNA signals were 181% and not significantly changed, respectively. Confocal laserscan immunohistochemistry and quantitative immunogold cytochemistry showed that MCT1 density was much higher in CHF than in Sham both at the surface membrane and in the intercalated disk. In CHF, a novel intracellular pool of MCT1 appeared to be associated with cisternae, some close to the T tubules. In contrast, connexin43 particles, seen exclusively at gap junctions, were substantially fewer. Maximum lactate uptake was 107+/-15 mmol. L(-1). min(-1) in CHF and 42+/-6 mmol. L(-1). min(-1) in Sham cells (P<0.05). The K(m) values were between 7 and 9 mmol/L (P=NS).


CONCLUSIONS
In cardiomyocytes from CHF rats, (1) the amount of functional MCT1 in the sarcolemma, including in the intercalated disk, is increased several-fold; (2) a new intracellular pool of MCT1 appears; (3) another disk protein, connexin43, is much reduced; and (4) increased reliance on lactate and other monocarboxylates (eg, pyruvate) could provide tight metabolic control of high-energy phosphates.
Jóhannsson
E
E
Department of Anatomy, Institute of Basic Medical Sciences, Institute for Experimental Medical Research, Ullevaal Hospital, University of Oslo, Oslo, Norway.
Lunde
P K
PK
Heddle
C
C
Sjaastad
I
I
Thomas
M J
MJ
Bergersen
L
L
Halestrap
A P
AP
Blackstad
T W
TW
Ottersen
O P
OP
Sejersted
O M
OM
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology; D007773:Lactates / Q000493:pharmacokinetics; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D027501:Monocarboxylic Acid Transporters; D009206:Myocardium / Q000737:chemistry* / Q000473:pathology / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
D002352:Carrier Proteins; D007773:Lactates; D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger