An alteration in calcium (Ca2+) mobilisation is believed to play an important physiological role in diabetes-induced cardiomyopathy (Ha et al. 1999). In this study we have investigated the role of Ca2+ mobilisation in ventricular myocytes from streptozotocin (STZ)-induced diabetic rats compared with age-matched controls. STZ (60 mg kg-1) was administered intraperitoneally (I.P.) to male Wistar rats (250Ð300 g). Animals were humanely killed by a blow to the head followed by cervical dislocation and ventricular myocytes were isolated by a combination of enzymatic and mechanical dispersal techniques (Howarth & Levi, 1998). Ca2+ transients were measured at 35Ð37 °C in fura-2-loaded cells by fluorescence photometry. Cells were superfused with a normal Tyrode (NT) solution containing 1 mM Ca2+. In some experiments, following a train of steady-state Ca2+ transients, electrical stimulation was abbreviated and caffeine (20 mM) was rapidly applied to release Ca2+ from the sarcoplasmic reticulum (SR). At 8Ð12 weeks after STZ treatment blood glucose levels in diabetic (mean ± S.E.M., 565.7 ± 22.9 mg dl-1, n = 5) animals were significantly higher (P < 0.01; independent samples t test) compared with controls (98.4 ± 3.9 mg dl-1, n = 5). Other characteristics of diabetic animals included significantly (P < 0.01) reduced body weight and heart weight. Previous experiments in our laboratory have demonstrated a significant (P < 0.05) increase in the amplitude and the time-to-peak (tpk) contraction in myocytes from STZ-treated compared with controls (Howarth et al. 2001).
The tpk of electrically evoked Ca2+ transients was not significantly altered by STZ-induced diabetes. However, the time from peak to half-relaxation of the Ca2+ transient was significantly (P < 0.01) longer in myocytes from diabetic (245.4 ± 8 ms, n = 24) compared with control (206.4 ± 9 ms, n = 24) rats (Fig. 1A). The fractional SR Ca2+ release following rapid application of caffeine was unaltered by STZ treatment. The rate of recovery of the Ca2+ transients, after resumption of electrical stimulation (Fig. 1B), was significantly (P < 0.05) faster in myocytes from diabetic (3.3 X 10-3 ± 0.3 X 10-3 ratio units s-1, n = 18) compared with control (2.2 X 10-3 ± 0.2 X 10-3 340/380 ratio units s-1, n = 9) rats. These results indicate that STZ-induced diabetes is associated with altered Ca2+ transport in the heart.
This work was supported by the British Heart Foundation.
All procedures accord with current national guidelines.