Hormone regulation of cardiac energy metabolism. I. Creatine transport across cell membranes of euthyroid and hyperthyroid rat heart.
Hyperthyroid rat heart was studied with the purpose of identifying the mechanism for the significant decrease in total creatine (free creatine plus phosphocreatine) observed in this pathology and its consequences on heart function. Administration of L-thyroxine in doses of 50-100 micrograms/100 g of body weight during a week resulted in a reversible decrease of the total creatine by 40-50%. Simultaneously, remarkable changes in the creatine transport system across the cardiac cell membranes were observed: both the maximal rate of its active uptake and its passive movement along its concentration gradient were enhanced. In euthyroid hearts, the parameters of creatine uptake (Km approximately or equal to 0.05 mM, Vmax = 20 nmole/min/g dry weight) were similar to those for skeletal muscle and the passive movement of creatine was negligible. In hyperthyroid hearts the latter rate was enhanced to 0.4 mumole min/g dry weight, this showing reversible damages in the cell membrane structure induced by L-thyroxine. This conclusion is consistent with observed penetration of colloidal lanthanum into the cells of hyperthyroid hearts. Perfusion of hyperthyroid rat hearts with 50 mM creatine significantly restored creatine content in the cells, Hyperthyroid hearts with decreased creatine content were found to develop ischemic contracture more rapidly and in higher extent than the euthyroid hearts. Increased sensitivity to ischemic damage may be related to decreased efficiency of energy channeling via phosphocreatine pathway.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism; D003401:Creatine / Q000378:metabolism*; D004734:Energy Metabolism; D006980:Hyperthyroidism / Q000378:metabolism*; D007700:Kinetics; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013963:Thyroid Hormones / Q000502:physiology*; D013974:Thyroxine / Q000494:pharmacology; D013997:Time Factors
D013963:Thyroid Hormones; D010725:Phosphocreatine; D003401:Creatine; D013974:Thyroxine