Shortening and intracellular Ca2+ in ventricular myocytes and expression of genes encoding cardiac muscle proteins in early onset type 2 diabetic Goto–Kakizaki rats

There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus. Cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. Contractile dysfunction, associated with disturbances in excitation–contraction coupling, has been widely demonstr...

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Bibliographic Details
Published in:Experimental physiology 2012-12, Vol.97 (12), p.1281-1291
Main Authors: Salem, K. A., Adrian, T. E., Qureshi, M. A., Parekh, K., Oz, M., Howarth, F. C.
Format: Article
Language:English
Subjects:
Animals
Blood Glucose - metabolism
Calcium - metabolism
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - genetics
Disease Models, Animal
Excitation Contraction Coupling - genetics
Fasting - blood
Gene Expression Regulation
Male
Muscle Proteins - genetics
Muscle Proteins - metabolism
Myocardial Contraction - genetics
Myocytes, Cardiac - metabolism
Rats
Rats, Wistar
Real-Time Polymerase Chain Reaction
Time Factors
Ventricular Dysfunction, Left - blood
Ventricular Dysfunction, Left - etiology
Ventricular Dysfunction, Left - genetics
Ventricular Dysfunction, Left - physiopathology
Ventricular Function, Left - genetics
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Summary:There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus. Cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. Contractile dysfunction, associated with disturbances in excitation–contraction coupling, has been widely demonstrated in the diabetic heart. The aim of this study was to investigate the pattern of cardiac muscle genes that are involved in the process of excitation–contraction coupling in the hearts of early onset (8–10 weeks of age) type 2 diabetic Goto–Kakizaki (GK) rats. Gene expression was assessed in ventricular muscle with real‐time RT‐PCR; shortening and intracellular Ca2+ were measured in ventricular myocytes with video edge detection and fluorescence photometry, respectively. The general characteristics of the GK rats included elevated fasting and non‐fasting blood glucose and blood glucose at 120 min following a glucose challenge. Expression of genes encoding cardiac muscle proteins (Myh6/7, Mybpc3, Myl1/3, Actc1, Tnni3, Tnn2, Tpm1/2/4 and Dbi) and intercellular proteins (Gja1/4/5/7, Dsp and Cav1/3) were unaltered in GK ventricle compared with control ventricle. The expression of genes encoding some membrane pumps and exchange proteins was unaltered (Atp1a1/2, Atp1b1 and Slc8a1), whilst others were either upregulated (Atp1a3, relative expression 2.61 ± 0.69 versus 0.84 ± 0.23) or downregulated (Slc9a1, 0.62 ± 0.07 versus 1.08 ± 0.08) in GK ventricle compared with control ventricle. The expression of genes encoding some calcium (Cacna1c/1g, Cacna2d1/2d2 and Cacnb1/b2), sodium (Scn5a) and potassium channels (Kcna3/5, Kcnj3/5/8/11/12, Kchip2, Kcnab1, Kcnb1, Kcnd1/2/3, Kcne1/4, Kcnq1, Kcng2, Kcnh2, Kcnk3 and Kcnn2) were unaltered, whilst others were either upregulated (Cacna1h, 0.95 ± 0.16 versus 0.47 ± 0.09; Scn1b, 1.84 ± 0.16 versus 1.11 ± 0.11; and Hcn2, 1.55 ± 0.15 versus 1.03 ± 0.08) or downregulated (Hcn4, 0.16 ± 0.03 versus 0.37 ± 0.08; Kcna2, 0.35 ± 0.03 versus 0.80 ± 0.11; Kcna4, 0.79 ± 0.25 versus 1.90 ± 0.26; and Kcnj2, 0.52 ± 0.07 versus 0.78 ± 0.08) in GK ventricle compared with control ventricle. The amplitude of ventricular myocyte shortening and the intracellular Ca2+ transient were unaltered; however, the time‐to‐peak shortening was prolonged and time‐to‐half decay of the Ca2+ transient was shortened in GK myocytes compared with control myocytes. The results of this study demonstrate changes in expression of genes encoding various excitation–contracti
ISSN:0958-0670
1469-445X
DOI:10.1113/expphysiol.2012.066639