Altered Calcium Homeostasis Does Not Explain the Contractile Deficit of Diabetic Cardiomyopathy
Open Access
- 1 August 2008
- journal article
- Published by American Diabetes Association in Diabetes
- Vol. 57 (8), 2158-2166
- https://doi.org/10.2337/db08-0140
Abstract
OBJECTIVE—This study examines the extent to which the contractile deficit of diabetic cardiomyopathy is due to altered Ca2+ homeostasis. RESEARCH DESIGN AND METHODS—Measurements of isometric force and intracellular calcium ([Ca2+]i, using fura-2/AM) were made in left ventricular (LV) trabeculae from rats with streptozotocin-induced diabetes and age-matched siblings. RESULTS—At 1.5 mmol/l [Ca2+]o, 37°C, and 5-Hz stimulation frequency, peak stress was depressed in diabetic rats (10 ± 1 vs. 17 ± 2 mN/mm2 in controls; P < 0.05) with a slower time to peak stress (77 ± 3 vs. 67 ± 2 ms; P < 0.01) and time to 90% relaxation (76 ± 7 vs. 56 ± 3 ms; P < 0.05). No difference was found between groups for either resting or peak Ca2+, but the Ca2+ transient was slower in time to peak (39 ± 2 vs. 34 ± 1 ms) and decay (time constant, 61 ± 3 vs. 49 ± 3 ms). Diabetic rats had a longer LV action potential (APD50, 98 ± 5 vs. 62 ± 5 ms; P < 0.0001). Western blotting showed that diabetic rats had a reduced expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a, with no difference in expression of the Na+/Ca2+ exchanger. Immunohistochemistry of LV free wall showed that type I collagen was increased in diabetic rats (diabetic 7.1 ± 0.1%, control 12.7 ± 0.1%; P < 0.01), and F-actin content reduced (diabetic 56.9 ± 0.6%; control 61.7 ± 0.4%; P < 0.0001) with a disrupted structure. CONCLUSIONS—We find no evidence to support the idea that altered Ca2+ homeostasis underlies the contractile deficit of diabetic cardiomyopathy. The slower action potential and reduced SERCA2a expression can explain the slower Ca2+ transient kinetics in diabetic rats but not the contractile deficit. Instead, we suggest that the observed LV remodeling may play a crucial role.Keywords
This publication has 42 references indexed in Scilit:
- Diabetic Cardiomyopathy RevisitedCell Metabolism, 2007
- Effect of Streptozotocin-Induced Type 1 Diabetes Mellitus on Contraction, Calcium Transient, and Cation Contents in the Isolated Rat HeartAnnals of the New York Academy of Sciences, 2006
- Animal models of diabetes mellitusDiabetic Medicine, 2005
- Streptozotocin-induced Changes in Cardiac Gene Expression in the Absence of Severe Contractile DysfunctionJournal of Molecular and Cellular Cardiology, 2000
- The relationship between contractile force and intracellular [Ca2+] in intact rat cardiac trabeculae.The Journal of general physiology, 1995
- Action potentials and potassium currents in rat ventricular muscle during experimental diabetesJournal of Molecular and Cellular Cardiology, 1992
- Kinetics, stoichiometry and role of the Na–Ca exchange mechanism in isolated cardiac myocytesNature, 1990
- Spontaneous calcium release from the sarcoplasmic reticulum in myocardial cells: mechanisms and consequencesCell Calcium, 1988
- Effect of Membrane Potential Changes on the Calcium Transient in Single Rat Cardiac Muscle CellsScience, 1987
- New type of cardiomyopathy associated with diabetic glomerulosclerosisThe American Journal of Cardiology, 1972