Decreased L-carnitine transport in mechanically overloaded rat hearts.
The transport of L[14C] carnitine was studied in rat hearts with a three-month-old aorto-caval fistula. Tissue TG content was determined in order to assess the state of FFA utilization. The hearts were perfused with a bicarbonate buffer containing 11 mM glucose and variable concentrations (10-200 microM) of L[14C] carnitine. In some experiments, the active component of carnitine transport was suppressed by the adjunction of 0.05 mM mersalyl acid. The subtraction of passive from total transport allowed us to reconstruct the saturation curves of the net active transport of L-carnitine. Our results suggest that at physiological carnitine concentration (50 microM) the uptake of L-carnitine is significantly depressed in mechanically overloaded hearts. These changes are not related to alterations of coronary perfusion, since coronary flow rates (ml/min/g dry wt) are quite comparable in both groups tested. According to the Lineweaver-Burk analysis of the kinetics of saturable transport, the affinity of the membrane carrier for L-carnitine is considerably diminished in the overloaded hearts (Km[carnitine] 125 instead of 83 microM). The alterations of the kinetics of carnitine transport do not seems to be related to the decrease of the transmembrane gradient of sodium: the intracellular sodium content of the hypertrophied, but non-failing, hearts is quite similar to that of control hearts. In addition, carnitine deficiency does not lead to TG accumulation, at least under in situ conditions.
el Alaoui-Talibi
Z
Z
I.N.S.E.R.M. U2, Hôpital Léon Bernard, Limeil-Grévannes, France.
Moravec
J
J
D000818:Animals; D001692:Biological Transport; D002331:Carnitine / Q000378:metabolism*; D005260:Female; D006331:Heart Diseases / Q000378:metabolism*; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D002331:Carnitine