Effects of streptozotocin-induced diabetes on contraction and calcium transport in rat ventricular cardiomyocytes

Cardiovascular diseases are the major cause of morbidity and mortality in diabetic patients. Contractile function of the heart is frequently compromised in the clinical setting and in experimental models of diabetes mellitus (DM). This article investigated the effect of streptozotocin (STZ)-induced type 1 DMon contraction, L-type calcium (Ca²⁺) current (I_Ca2+L), and on cytosolic calcium concentrations [Ca²⁺]_i in ventricular myocytes of the rat heart. After 4-10 weeks of STZ treatment, blood glucose levels in diabetic animals were significantly (P < 0.05) higher compared to age-matched controls. Diabetic rats have significantly (P < 0.05) reduced body, reduced heart weight, and reduced viability of ventricular myocytes compared to controls. The amplitude of I_Ca2+L and amplitude of contraction were significantly reduced (P < 0.05) at test potentials in the range -10 mV to +20 mV and -30 mV to +40 mV, respectively, in myocytes from diabetic animals compared to age-matched controls. Moreover, there was a significant (P < 0.05) delay in electrically stimulated and caffeine-evoked time to half relaxation of the Ca²⁺ transient in myocytes from diabetic animals compared to controls. A similar effect was obtained in myocytes treated with a combination of caffeine and nickel chloride (NiCl₂). It is concluded that the diabetes-induced voltage-dependent decrease in contraction is associated with reduced Ca²⁺ channel activities and prolonged diastolic cytosolic Ca²⁺ compared to age-matched control. Taken together, the results suggest that Ca²⁺ homeostasis is deranged during DM and this may be expressed at the level of the Na⁺/Ca ²⁺ exchanger.