CARNITINE TRANSPORT IN ISOLATED ADULT-RAT HEART MYOCYTES AND THE EFFECT OF 7,8-DIOH CHLORPROMAZINE

The carnitine transport system was studied in isolated adult rat heart myocytes able to tolerate physiological concentrations of Ca. Carnitine uptake occurred against a concentration gradient and was inhibited by 2,4-dinitrophenol (2,4-DNP). The transport system had a KM of 60 .mu.M and a Vmax of 110 pmol/mg protein per h. The carnitine precursor deoxycarnitine, acetylcarnitine and the D and L isomers were effective inhibitors of uptake. The transport of carnitine was not dependent on Na ions, but was stimulated by decreasing concentrations of Ca ions. Decreased uptake was observed in the presence of .beta.-adrenergic agonists and antagonists, dibutyryl cAMP, local anesthetics and ouabain. No significant alteration of uptake was effected by atropine, carbachol or a variety of tricyclic agents. The auto-oxidation product of 7,8-dihydroxychlorpromazine (7,8-diOH CPZ) decreased carnitine efflux from myocytes, which were highly permeable to low MW compounds. This effect was not substrate specific, and is discussed as possibly resulting from a change in the arrangement or state of polymerization of subcellular structural components.