Involvement of long chain acylcarnitines in the depression of cardiac sarcoplasmic reticulum function in diabetic rats *1. Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada, V6T 1W5

1982 ◽  
Vol 14 ◽  
pp. 46
Keyword(s):  
British Columbia ◽  
Sarcoplasmic Reticulum ◽  
Diabetic Rats ◽  
Pharmaceutical Sciences ◽  
Cardiac Sarcoplasmic Reticulum ◽  
University Of British Columbia ◽  
Pharmacology And Toxicology ◽  
Long Chain

The effect of alloxan- and streptozotocin-induced diabetes on calcium transport in rat cardiac sarcoplasmic reticulum. The possible involvement of long chain acylcarnitines

1983 ◽  
Vol 61 (5) ◽  
pp. 439-448 ◽  
Author(s):  
Gary D. Lopaschuk ◽  
Sidney Katz ◽  
John H. McNeill
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Heart Function ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Microsomal Preparation ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Gradual Onset ◽  
Female Wistar Rats ◽  
Streptozotocin Induced Diabetes ◽  
Long Chain

Isolated working hearts from diabetic rats have a decreased ability to respond to increasing preload or afterload. The ability of cardiac sarcoplasmic reticulum to transport Ca2+ was examined in diabetic rats. Hearts were obtained from female Wistar rats 120 days or 7 days after the induction of diabetes by a single I.V. injection of either alloxan (65 mg/kg) or streptozotocin (60 mg/kg). At all Ca2+ concentrations tested (0.2–5.0 μM free Ca2+) cardiac sarcoplasmic reticulum from 120-day diabetic rats showed a significant decrease in the rate of ATP-dependent tris-oxalate facilitated Ca2+ transport (62–73% of control). This was accompanied by a decrease in Ca2+ ATPase activity. The levels of long chain acylcarnitines associated with the microsomal sarcoplasmic reticulum preparation from 120-day diabetic rats were significantly higher than those present in sarcoplasmic reticulum from control rats. Palmitylcarnitine, the most abundant of the long chain acylcarnitines, in concentrations < 7 μM was found to be a potent time-dependent inhibitor of Ca2+ transport in both control and diabetic rat sarcoplasmic reticulum preparations; inhibition of Ca2+ transport was found to be more marked in the control preparations. This would indicate that a degree of inhibition produced by the high endogenous levels of palmitylcarnitine may already be present in the diabetic rat preparations. Cardiac sarcoplasmic reticulum prepared from acutely diabetic rats (7 days) did not show any decrease in Ca2+ transport ability. Levels of long chain acylcarnitines associated with the microsomal preparation enriched in sarcoplasmic reticulum were also unchanged. These findings suggest that the alteration in heart function in 120-day diabetic rats may be due to the buildup of cellular long chain acylcarnitines which inhibit sarcoplasmic reticulum Ca2+ transport. The absence of any change in Ca2+-transport activity or levels of long chain acylcarnitines at 7 days suggests that the alterations seen in 120-day diabetic rats must be of gradual onset.

Sarcoplasmic reticulum Ca2+ transport and long chain acylcarnitines in hyperthyroidism

1988 ◽  
Vol 66 (2) ◽  
pp. 159-165 ◽  
Author(s):  
Shawn C. Black ◽  
John H. McNeill ◽  
Sidney Katz
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Transport ◽  
Wistar Rats ◽  
Free Calcium ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Calcium Dependent ◽  
Endogenous Level ◽  
Male Wistar Rats ◽  
Carnitine Derivatives ◽  
Long Chain

Male Wistar rats were treated with L-3,5,3′-triiodothyronine (T3) (500 μg∙kg∙−1∙day−1) for 3 days. Cardiac sarcoplasmic reticulum (SR) was isolated at several time points during the induction of the hyperthyroid state and calcium transport and the levels of carnitine derivatives were determined. Calcium transport was augmented at all free calcium concentrations assayed (0.1–5.3 μM) 24 h following a single dose of T3; at 48 and 72 h, calcium transport was further augmented. Calcium-dependent phosphoprotein levels were increased in the SR of the 48- and 72-h T3-treated groups. Total SR carnitine was reduced after 24, 48, and 72 h of treatment. Long chain acylcarnitine (LCAC) levels were decreased in T3-treated SR at 48 and 72 h. This study shows that calcium transport is increased in T3-treated rat heart SR and that this increase may be related to a reduction in the endogenous level of LCAC in the SR membrane.

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