title: Oxidative effects of selenite on rat ventricular contractility and Ca movements.
abstract: 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 > or = 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 disulfonic reducing agent dithiothreitol (DTT, 1 mM). Lowering temperature from 35 degrees to 22 degrees 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 degrees 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.
authors.affiliation: Department of Biophysics, Faculty of Medicine, University of Ankara, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Turan
authors.forename: M
authors.initials: M
authors.lastname: Désilets
authors.forename: L N
authors.initials: LN
authors.lastname: Açan
authors.forename: O
authors.initials: O
authors.lastname: Hotomaroglu
authors.forename: C
authors.initials: C
authors.lastname: Vannier
authors.forename: G
authors.initials: G
authors.lastname: Vassort
mesh_terms: D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018038:Sodium Selenite / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013439:Sulfhydryl Reagents / Q000494:pharmacology
chemical_list: D013439:Sulfhydryl Reagents; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D018038:Sodium Selenite; D002118:Calcium; D004229:Dithiothreitol