Selenium-induced alterations in ionic currents of rat cardiomyocytes

In the present study, rats were treated with sodium selenite (5 μmol/kg body weight/day, ip) for 4 weeks and the parameters of contractile activity, action potential, L-type Ca2+-current (ICaL), as well as transient outward (Ito), inward rectifier (IK1), and steady state (Iss) K+-currents were investigated. Sodium selenite treatment increased rat blood glucose level and lowered plasma insulin level, significantly. This treatment also caused slightly prolongation in action potential with no significant effects on spontaneous contraction parameters and intracellular Ca2+ transients of the heart preparations. These effects were associated with marked alterations in the kinetics of both ICaL and Ito including a significant slowing in both inactivation time constants of ICaL and a significant shift to negative potential at half-inactivation of these channels without any change in the current density. Also, there was a significantly faster inactivation of Ito and no shift in half-inactivation of this channel without any change in its current density. Consequently, there was a ∼50% increase in total charges carried by Ca2+ current and ∼50% decrease in total charges carried by K+ currents of the treated rat cardiomyocytes. Additionally we observed a significant inhibition in IK1 density in treated rat cardiomyocytes. Oxidized glutathione level was significantly increased (70%) while the observed decrease in reduced glutathione was much less. Since a shift in redox state of regulatory proteins is related with cell dysfunction, selenium-induced increase in blood glucose and decrease in plasma insulin may correlate these alterations. These alterations, in the kinetics of the channels and in IK1 density, might lead to proarrhythmic effect of chronic selenium supplementation.