Upregulation of the cardiac monocarboxylate transporter MCT1 in a rat model of congestive heart failure

Background-Cardiac metabolism becomes more dependent on carbohydrates in co ngestive heart failure (CHF), and lactate may be used as an important respi ratory 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 intercalate d disk. Methods and 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 correspo nding mRNA signals were 181% and not significantly changed, respectively. C onfocal laserscan immunohistochemistry and quantitative immunogold cytochem istry 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 intracel lular pool of MCT1 appeared to be associated with cisternae, some close to the T tubules. In contrast, connexin43 particles, seen exclusively at gap j unctions, were substantially fewer. Maximum lactate uptake was 107 +/- 15 m mol.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 M CT1 in the sarcolemma, including in the intercalated disk, is increased sev eral-fold; (2) a new intracellular pool of MCT1 appears; (3) another disk p rotein, connexin43, is much reduced; and (4) increased reliance on lactate and other monocarboxylates (eg, pyruvate) could provide tight metabolic con trol of high-energy phosphates.