Akademik Veri Yönetim Sistemi
Cardiovascular Research, cilt.32, sa.2, ss.351-361, 1996 (SCI-Expanded)
Objective: The study aimed at characterizing the effects of selenite, known for its reactivity with thiols, on cardiac contractility and excitation-contraction coupling. Methods: The inotropic effects of selenite were studied on rat papillary muscles. Freshly isolated rat ventricular myocytes were used to determine the selenite-induced alterations in thiol contents, free Ca2+ levels (in fura-2 loaded cells), Ca2+ currents and contractile properties of skinned cells. Results: Selenite, at concentrations ≤0.1 mM, affected muscle contractions by inducing a transient positive inotropic effect (up to 120 ± 3% of control in 1 mM selenite) followed by a gradual decline of developed tension together with an increase in resting tension (respectively to 37 ± 3 and 166 ± 5% of their control values after 20 min exposure). These changes, irreversible on washout, could be reversed by the disulfide reducing agent dithiothreitol (DTT, 1 mM). Lowering temperature from 35° to 22°C or preincubating the muscles with the disulfonic stilbene SITS (0.2 mM) completely prevented the selenite-induced transient positive inotropy and rise in resting tension. In isolated myocytes, 10 min exposure to 1 mM selenite induced a 40 ± 9% decrease of total sulfhydryl content. At this concentration, selenite rapidly caused a rise of basal [Ca2+](i) together with a diminution of the Ca2+ spike amplitude (respectively to 165 ± 15 and 45 ± 9% of their control values after 5 min exposure). In addition, selenite significantly enhanced at each Ca2+ concentration the force generated by skinned myocytes. Ca2+ currents, measured at 22°C, decreased by 28 ± 8% in the presence of 1 mM selenite. These effects were reversed by DTT. Conclusions: The results demonstrate that selenite, through alterations of cellular thiol redox status, induced a dual action on muscle contraction that can be imputed to a combined action on Ca2+ channels, Ca2+ transporters and contractile proteins. Extracellular negative effects of selenite are due to a partial reduction of Ca2+ current magnitude. Intracellular effects are mediated both by a diminution of Ca2+ handing by intracellular organelles and by a sensitization of the contractile to Ca2+ ions. The results further indicate that selenite uptake into the cardiac cells occurs mainly through the temperature-sensitive anion exchanger.