Calcium signaling in endocardial and epicardial ventricular myocytes from streptozotocin-induced diabetic rats

Aims/Introduction: Abnormalities in Ca²⁺ signaling have a key role in hemodynamic dysfunction in diabetic heart. The purpose of this study was to explore the effects of streptozotocin (STZ)-induced diabetes on Ca²⁺ signaling in epicardial (EPI) and endocardial (ENDO) cells of the left ventricle after 5–6 months of STZ injection. Materials and Methods: Whole-cell patch clamp was used to measure the L-type Ca²⁺ channel (LTCC) and Na⁺/Ca²⁺ exchanger currents. Fluorescence photometry techniques were used to measure intracellular free Ca²⁺ concentration. Results: Although the LTCC current was not significantly altered, the amplitude of Ca²⁺ transients increased significantly in EPI-STZ and ENDO-STZ compared with controls. Time to peak LTCC current, time to peak Ca²⁺ transient, time to half decay of LTCC current and time to half decay of Ca²⁺ transients were not significantly changed in EPI-STZ and ENDO-STZ myocytes compared with controls. The Na⁺/Ca²⁺ exchanger current was significantly smaller in EPI-STZ and in ENDO-STZ compared with controls. Conclusions: STZ-induced diabetes resulted in an increase in amplitude of Ca²⁺ transients in EPI and ENDO myocytes that was independent of the LTCC current. Such an effect can be attributed, at least in part, to the dysfunction of the Na⁺/Ca²⁺ exchanger. Additional studies are warranted to improve our understanding of the regional impact of diabetes on Ca²⁺ signaling, which will facilitate the discovery of new targeted treatments for diabetic cardiomyopathy.