Alterations in Ca(2+)-channels during the development of diabetic cardiomyopathy.
In order to examine the status of Ca2+ channels in heart sarcolemma during the development of diabetes, rats were injected intravenously with 65 mg/kg streptozotocin and hearts were removed 1, 3 and 8 weeks later. Crude membranes from the ventricular muscle were prepared and the specific binding of 3H-nitrendipine was studied by employing different concentrations of this Ca(2+)-antagonist. A significant decrease in both dissociation constant and maximal number of 3H-nitrendipine binding was observed in 3 and 8 weeks diabetic preparations. No such alterations were evident in diabetic brain membranes. Treatment of diabetic animals with insulin prevented the occurrence of these changes in the myocardium. The altered 3H-nitrendipine binding characteristics in diabetic heart membranes may not be due to the high levels of circulating catecholamines in this experimental model because no such changes were seen upon injecting a high dose (40 mg/kg) of isoproterenol in rats for 24 hr. The reduced number of 3H-nitrendipine binding sites may decrease Ca(2+)-influx through voltage sensitive Ca2+ channels and partly explain the depressed cardiac contractile force development in chronic diabetes whereas the increased affinity of Ca2+ channels may partly explain the increased sensitivity of diabetic heart to Ca2+.
Lee
S L
SL
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Manitoba, Canada.
Ostadalova
I
I
Kolar
F
F
Dhalla
N S
NS
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D009202:Cardiomyopathies / Q000209:etiology* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D001786:Blood Glucose; D015220:Calcium Channels; D007328:Insulin; D011978:Receptors, Nicotinic; D009568:Nitrendipine; D014700:Verapamil; D000252:Calcium-Transporting ATPases; D007545:Isoproterenol; D002118:Calcium