Contractile dysfunction has been reported in ventricular myocytes from the streptozotocin (STZ)-induced diabetic rat model, which include a prolonged time course and reduced amplitude of contraction (Ren & Davidoff, 1997; Howarth et al. 2000), although the role of intracellular Ca²⁺ regulation in these effects is still unclear. Volatile general anaesthetics (e.g. halothane) in addition to inducing unconsciousness, also have a potent negative inotropic effect on the heart (Davies et al. 1999) linked to altered Ca²⁺ regulation. The aim was to investigate the role of altered Ca²⁺ regulation in contractile dysfunction in myocytes from the STZ-induced diabetic rat in the absence and presence of a clinically relevant dose of halothane.

Diabetes was induced in male Wistar rats by I.P. injection of STZ (60 mg kg^-1) and animals killed humanely 8-12 weeks following treatment (methodology approved by Faculty of Medicine and Health Sciences Animal Ethics Committee). Characteristics of electrically evoked cytosolic Ca²⁺ transients and caffeine-evoked Ca²⁺ transients, which provide a measure of sarcoplasmic reticulum (SR) Ca²⁺ content, were measured in fura-2-loaded control and STZ myocytes in the absence and presence of 0.6 mM halothane at 35-36°C. Data are expressed as means ± S.E.M. (n cells) and statistical comparisons made using either unpaired or paired t tests as appropriate.

The amplitude of the electrically evoked Ca²⁺ transient was significantly (P < 0.001) reduced (by ~45 %) in STZ compared with control myocytes. The time course of the Ca²⁺ transient was prolonged (P < 0.001) following STZ treatment; time to peak was 72 ± 4 ms (30) vs. 55 ± 3 ms (34) and time to half-relaxation was 220 ± 9 ms vs. 158 ± 8 ms in STZ and control myocytes, respectively. Halothane reduced (P < 0.001) Ca²⁺ transient amplitude in both STZ and control myocytes; however, the relative magnitude of this reduction was not different between control and STZ myocytes (P > 0.05).

The amplitude of the caffeine-evoked Ca²⁺ transient was not significantly altered by STZ treatment. In control cells, halothane significantly reduced SR Ca²⁺ content by 28 ± 4 % (P < 0.001) and the magnitude of this reduction was not significantly different (P > 0.05) in STZ myocytes. Fractional SR Ca²⁺ release was increased to a similar extent in both STZ and control myocytes by halothane. These data suggest that altered mechanisms of Ca²⁺ transport might underlie the contractile abnormalities reported in myocytes from STZ-treated rats but these do not appear to be further complicated by halothane.

All procedures accord with current local guidelines.