Alloxan reduces amplitude of ventricular myocyte shortening and intracellular [Ca.sup.2+] without altering L-type [Ca.sup.2+] current, sarcoplasmic reticulum [Ca.sup.2+] content or myofilament sensitivity to [Ca.sup.2+] in Wistar rats

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 [Ca.sup.2+] transport. Amplitude of myocyte shortening was reduced in a dose-dependent manner as the concentration of alloxan was increased in the range [10.sup.-7]-[10.sup.-4] M. Amplitude of shortening was reduced (56.8 [+ or -] 6.6%, n = 27) by [10.sup.-6] M alloxan and was partially reversed during a 10 min washout. Amplitude of the [Ca.sup.2+] transient was also reduced (79.7 [+ or -] 2.9%, n = 29) by [10.sup.-6] M alloxan. Caffeine-evoked sarcoplasmic reticulum [Ca.sup.2+] release, fractional release of [Ca.sup.2+], assessed by comparing the amplitude of electrically evoked with that of caffeine-evoked [Ca.sup.2+] 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 [Ca.sup.2+] current was not altered by alloxan. Alterations in sarcoplasmic reticulum [Ca.sup.2+] transport, myofilament sensitivity to [Ca.sup.2+], and L-type [Ca.sup.2+] current do not appear to underlie the negative inotropic effects of alloxan. Keywords Alloxan * Heart * Cardiac muscle contraction * Intracellular calcium * Ventricular myocytes