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.
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(2+) 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 Ca(2+) transient was also reduced (79.7 +/- 2.9%, n = 29) by 10(-6) M alloxan. Caffeine-evoked sarcoplasmic reticulum Ca(2+) release, fractional release of Ca(2+), assessed by comparing the amplitude of electrically evoked with that of caffeine-evoked Ca(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(2+) current was not altered by alloxan. Alterations in sarcoplasmic reticulum Ca(2+) transport, myofilament sensitivity to Ca(2+), and L-type Ca(2+) current do not appear to underlie the negative inotropic effects of alloxan.
Salem
Khawla Abdulla
KA
Department of Physiology, Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, UAE.
Qureshi
Anwar
A
Ljubisavijevic
Milos
M
Oz
Murat
M
Isaev
Dmytro
D
Hussain
Munir
M
Howarth
Frank Christopher
FC
D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D000496:Alloxan / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D020746:Calcium Channels, L-Type; D002110:Caffeine; D000496:Alloxan; D002118:Calcium