Cellular functions of diabetic cardiomyocytes: contractility, rapid-cooling contracture, and ryanodine binding.
To study the mechanisms of cardiac dysfunction in experimental diabetes, adult rat cardiomyocyte shortening (measured with a video edge-detector system), the sarcoplasmic reticulum (SR) Ca2+ content [assessed by rapid-cooling contracture (RCC) and caffeine contracture (CC)] was examined. Ryanodine binding to the SR Ca(2+)-release channel of myocardium homogenate was also studied. Myocytes from diabetic rats showed depressed shortening (44% decrease compared with controls), reduced maximum rates of shortening and relengthening (58 and 56% decrease, respectively), and prolonged time to peak shortening (47% increase). RCCs and CCs from diabetic cells were 68 and 75% of the control values, respectively. Most of these cardiomyocyte abnormalities were corrected by daily insulin treatment in the diabetic rats. Ryanodine binding parameters indicated that the number of high-affinity binding sites was decreased in diabetic hearts. These data suggest that changes in contractile parameters as measured in diabetic myocytes are in good agreement with data obtained from intact heart or cardiac tissue preparations. Decreased SR Ca2+ content and reduced ryanodine binding sites indicate that the SR functions of storage and release of Ca2+ were depressed. This consequently may cause depressed contraction in diabetic hearts.
Yu
Z
Z
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Tibbits
G F
GF
McNeill
J H
JH
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006352:Heart Ventricles; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D001786:Blood Glucose; D015220:Calcium Channels; D007328:Insulin; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002110:Caffeine; D002118:Calcium