Selenium-induced alterations in ionic currents of rat cardiomyocytes

In the present study, rats were treated with sodium selenite (5 mumol/kg body weight/day, ip) for 4 weeks and the parameters of contractile activity, action potential, L-type Ca2+ -current (I-CaL), as well as transient outward (I-tO), inward rectifier (I-K1), and steady state (I-ss) 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 I-CaL and I-tO including a significant slowing in both inactivation time constants of I-CaL 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 It. and no shift in half-inactivation of this channel without any change in its current density. Consequently, there was a similar to50% increase in total charges carried by Ca2+ current and similar to50% decrease in total charges carried by K+ currents of the treated rat cardiomyocytes. Additionally we observed a significant inhibition in I-K1 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 I-K1 density, might lead to proarrhythmic effect of chronic selenium supplementation. (C) 2004 Elsevier Inc. All rights reserved.