Contractility of ventricular myocytes is well preserved despite altered mechanisms of [Ca.sup.2+] transport and a changing pattern of mRNA in aged type 2 Zucker diabetic fatty rat heart

• Published in: Molecular and cellular biochemistry 2012-02, Vol.361 (1-2), p.267
• Main Authors: Howarth, F.C, Qureshi, M.A, Hassan, Z, Isaev, D, Parekh, K, John, A, Oz, M, Raza, H, Adeghate, E, Adrian, T.E
• Format: Article
• Language: English
• Subjects: Blood sugar; Gene expression; Glucose metabolism; Health aspects; Messenger RNA; Muscle proteins; Type 2 diabetes
• ISSN: 0300-8177
• DOI: 10.1007/s11010-011-1112-y

There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The objective of the study was to investigate ventricular myocyte shortening, intracellular [Ca.sup.2+] signalling and expression of genes encoding cardiac muscle proteins in the aged Zucker diabetic fatty (ZDF) rat. There was a fourfold elevation in non-fasting blood glucose in ZDF rats (478.43 [+ or -] 29.22 mg/dl) compared to controls (108.22 [+ or -] 2.52 mg/dl). Amplitude of shortening, time to peak (TPK) and time to half (THALF) relaxation of shortening were unaltered in ZDF myocytes compared to age-matched controls. Amplitude and THALF decay of the [Ca.sup.2+] transient were unaltered; however, TPK [Ca.sup.2+] transient was prolonged in ZDF myocytes (70.0 [+ or -] 3.2 ms) compared to controls (58.4 [+ or -] 2.3 ms). Amplitude of the L-type [Ca.sup.2+] current was reduced across a wide range of test potentials (-30 to +40 mV) in ZDF myocytes compared to controls. Sarcoplasmic reticulum [Ca.sup.2+] content was unaltered in ZDF myocytes compared to controls. Expression of genes encoding cardiac muscle proteins, membrane [Ca.sup.2+] channels, and cell membrane ion transport and intracellular [Ca.sup.2+] transport proteins were variously altered. Myh6, Tnnt2, Cacna2d3, Slc9a1, and Atp2a2 were downregulated while Myl2, Cacna1g, Cacna1h, and Atp2a1 were upregulated in ZDF ventricle compared to controls. The results of this study have demonstrated that preserved ventricular myocyte shortening is associated with altered mechanisms of [Ca.sup.2+] transport and a changing pattern of genes encoding a variety of [Ca.sup.2+] signalling and cardiac muscle proteins in aged ZDF rat. Keywords Zucker diabetic fatty rat * Type 2 diabetes mellitus * Ventricular myocytes * Cardiac muscle contraction * Calcium transport * mRNA * Gene expression