Alloxan reduces amplitude of ventricular myocyte shortening and intracellular Ca²⁺ without altering L-type Ca²⁺ current, sarcoplasmic reticulum Ca²⁺ content or myofilament sensitivity to Ca²⁺ in Wistar rats

Abstract

Alloxan is widely used to induce diabetes mellitus in experimental animals. Recent studies have provided evidence that alloxan has direct actions on cardiac muscle contraction. The aim of this study was to further investigate the mechanisms underlying the effects of alloxan on ventricular myocyte shortening and intracellular Ca²⁺ transport. Amplitude of myocyte shortening was reduced in a dose-dependent manner as the concentration of alloxan was increased in the range 10⁻⁷–10⁻⁴ M. Amplitude of shortening was reduced (56.8 ± 6.6%, n = 27) by 10⁻⁶ M alloxan and was partially reversed during a 10 min washout. Amplitude of the Ca²⁺ transient was also reduced (79.7 ± 2.9%, n = 29) by 10⁻⁶ M alloxan. Caffeine-evoked sarcoplasmic reticulum Ca²⁺ release, fractional release of Ca²⁺, assessed by comparing the amplitude of electrically evoked with that of caffeine-evoked Ca²⁺ transients, and fura-2-cell length trajectory during the late stages of relaxation of myocyte twitch contraction were not significantly altered by alloxan. The amplitude of L-type Ca²⁺ current was not altered by alloxan. Alterations in sarcoplasmic reticulum Ca²⁺ transport, myofilament sensitivity to Ca²⁺, and L-type Ca²⁺ current do not appear to underlie the negative inotropic effects of alloxan.