The effects of low density lipoprotein on calcium transients in isolated rabbit cardiomyocytes.
The purpose of this study was to examine the effects of low density lipoprotein (LDL) on Ca2+ transients of isolated rabbit cardiomyocytes. Incubation of cardiomyocytes with > or = 1 mg of LDL cholesterol/ml of perfusion medium induced a slow (> or = 30 min) but significant increase (2-fold) in the cellular Ca2+ transient. The time course for the effect was similar to that observed for the accumulation of cholesterol in the cells. Using Dil- labeled LDL as a fluorescent marker for LDL interaction with the cardiomyocytes, it was concluded that LDL interacted via a receptor-mediated event, but probably this was not the primary mechanism whereby the lipid entered the cell. LDL-treated cells were resistant to the depressant actions for ryanodine, nicardipine, and dichlorobenzamil on the cellular Ca2+ transient. Lowering the extracellular Ca2+ concentration removed the stimulatory effect of LDL on the Ca2+ transient. It is concluded that LDL can induce an increase in the magnitude of the Ca2+ transient in isolated cardiomyocytes. This is a relatively slow process. The mechanism appears to involve a stimulation of a transsarcolemmal Ca2+ transport pathway. These findings have important implications for cardiac contractile function in hypercholesterolemic and drug-treated hypercholesterolemic subjects.
Liu
K
K
Ion Transport Laboratory, St. Boniface General Hospital Research Center, Winnipeg, Manitoba, Canada.
Pierce
G N
GN
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D003971:Diastole / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles; D007700:Kinetics; D008074:Lipoproteins / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000378:metabolism*; D009529:Nicardipine / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism*; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D013599:Systole / Q000187:drug effects; D013997:Time Factors
D002788:Cholesterol Esters; D008074:Lipoproteins; D010743:Phospholipids; C041470:3',4'-dichlorobenzamil; D012433:Ryanodine; D000584:Amiloride; D002784:Cholesterol; D009529:Nicardipine; D002118:Calcium