Contractility of ventricular myocytes is well preserved despite altered mechanisms of Ca 2+ transport and a changing pattern of mRNA in aged type 2 Zucker diabetic fatty rat heart F. C. Howarth • M. A. Qureshi • Z. Hassan • D. Isaev • K. Parekh • A. John • M. Oz • H. Raza • E. Adeghate • T. E. Adrian Received: 23 August 2011 / Accepted: 7 October 2011 / Published online: 19 October 2011 Ó Springer Science+Business Media, LLC. 2011 Abstract 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 mor- tality in diabetic patients. The objective of the study was to investigate ventricular myocyte shortening, intracellular Ca 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 glu- cose in ZDF rats (478.43 ± 29.22 mg/dl) compared to controls (108.22 ± 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 2? transient were unaltered; however, TPK Ca 2? tran- sient was prolonged in ZDF myocytes (70.0 ± 3.2 ms) compared to controls (58.4 ± 2.3 ms). Amplitude of the L-type Ca 2? current was reduced across a wide range of test potentials (-30 to ?40 mV) in ZDF myocytes com- pared to controls. Sarcoplasmic reticulum Ca 2? content was unaltered in ZDF myocytes compared to controls. Expression of genes encoding cardiac muscle proteins, membrane Ca 2? channels, and cell membrane ion transport and intracellular Ca 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 2? transport and a changing pattern of genes encoding a variety of Ca 2? signalling and cardiac muscle proteins in aged ZDF rat. Keywords Zucker diabetic fatty rat Á Type 2 diabetes mellitus Á Ventricular myocytes Á Cardiac muscle contraction Á Calcium transport Á mRNA Á Gene expression Introduction The total number of people with diabetes is projected to rise from 171 million in 2000 to 366 million in 2030 [1]. Type 2 diabetes mellitus has reached pandemic proportions and will continue to escalate. The association between type 2 diabetes and obesity is very strong and cardiovascular disease is the major cause of morbidity and mortality in diabetic patients [2, 3]. Clinical and pre-clinical studies using Doppler imaging, echocardiography, radionuclide angiography, and other techniques have demonstrated a variety of diastolic and systolic dysfunctions in type 2 diabetic patients. Hemo- dynamic abnormalities include reduced left ventricular ejection fraction, impaired myocardial velocity at early diastole, abnormal relaxation during the early filling phase, prolonged isovolumetric relaxation, lower peak systolic F. C. Howarth (&) Á M. A. Qureshi Á Z. Hassan Á K. Parekh Á T. E. Adrian Department of Physiology, Faculty of Medicine & Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, UAE e-mail: chris.howarth@uaeu.ac.ae D. Isaev Á M. Oz Department of Pharmacology, Faculty of Medicine & Health Sciences, United Arab Emirates University, Al Ain, UAE A. John Á H. Raza Department of Biochemistry, Faculty of Medicine & Health Sciences, United Arab Emirates University, Al Ain, UAE E. Adeghate Department of Anatomy, Faculty of Medicine & Health Sciences, United Arab Emirates University, Al Ain, UAE 123 Mol Cell Biochem (2012) 361:267–280 DOI 10.1007/s11010-011-1112-y