Voltage dependence of the Ca²⁺ transient in endocardial and epicardial myocytes from the left ventricle of Goto–Kakizaki type 2 diabetic rats

Diabetes mellitus is a major global health disorder and, currently, over 450 million people have diabetes with 90% suffering from type 2 diabetes. Left untreated, diabetes may lead to cardiovascular diseases which are a leading cause of death in diabetic patients. Calcium is the trigger and regulator of cardiac muscle contraction and derangement in cellular Ca²⁺ homeostasis, which can result in heart failure and sudden cardiac death. It is of paramount importance to investigate the regional involvement of Ca²⁺ in diabetes-induced cardiomyopathy. Therefore, the aim of this study was to investigate the voltage dependence of the Ca²⁺ transients in endocardial (ENDO) and epicardial (EPI) myocytes from the left ventricle of the Goto–Kakizaki (GK) rats, an experimental model of type 2 diabetes mellitus. Simultaneous measurement of L-type Ca²⁺ currents and Ca²⁺ transients was performed by whole-cell patch clamp techniques. GK rats displayed significantly increased heart weight, heart weight/body weight ratio, and non-fasting and fasting blood glucose compared to controls (CON). Although the voltage dependence of L-type Ca²⁺ current was unaltered, the voltage dependence of the Ca²⁺ transients was reduced to similar extents in EPI–GK and ENDO–GK compared to EPI–CON and ENDO–CON myocytes. TPK L-type Ca²⁺ current and Ca²⁺ transient were unaltered. THALF decay of L-type Ca²⁺ current was unaltered; however, THALF decay of the Ca²⁺ transient was shortened in ENDO and EPI myocytes from GK compared to CON rat hearts. In conclusion, the amplitude of L-type Ca²⁺ current was unaltered; however, the voltage dependence of the Ca²⁺ transient was reduced to similar extents in EPI and ENDO myocytes from GK rats compared to their respective controls, suggesting the possibility of dysfunctional sarcoplasmic reticulum Ca²⁺ transport in the GK diabetic rat hearts.