Selenium-induced alterations in ionic currents of rat cardiomyocytes
Selenium-induced alterations in ionic currents of rat cardiomyocytes
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DOI：
10.1016/j.bbrc.2004.12.003
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发表时间：
2005-02-04
影响因子：
3.1
通讯作者：
Turan, B
中科院分区：
文献类型：
--
作者：
Ayaz, M;Ozdemir, S;Turan, B
在本研究中，大鼠用亚硒酸钠（5 μ mol/kg体重/天，ip）处理4周，并研究了收缩活动，动作电位，L型钙电流（I-CaL），以及瞬时外向（I-tO），内向整流（I-K1）和稳态（I-ss）K+电流的参数。亚硒酸钠处理显著升高大鼠血糖水平，降低血浆胰岛素水平。该处理还导致动作电位略微延长，对心脏制备物的自发收缩参数和细胞内Ca 2+瞬变无显著影响。这些影响与I-CaL和I-tO的动力学显著改变有关，包括I-CaL的失活时间常数显著减慢，以及这些通道在半失活时向负电位的显著转变，而电流密度无任何变化。此外，It.的失活速度显著加快，并且在电流密度无任何变化的情况下，该通道的半失活没有发生变化。因此，有一个类似于50%的增加，总电荷携带的Ca 2+电流和类似于50%的减少，总电荷携带的K+电流的处理大鼠心肌细胞。另外，我们观察到在处理的大鼠心肌细胞中I-K1密度的显著抑制。氧化型谷胱甘肽水平显着增加（70%），而观察到的减少还原型谷胱甘肽是少得多。由于在调节蛋白的氧化还原状态的转变与细胞功能障碍，硒诱导的血糖升高和血浆胰岛素的降低可能与这些变化。这些改变，在通道的动力学和I-K1密度，可能会导致慢性补硒的promammic效应。(C)2004年爱思唯尔公司All rights reserved.
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.