Rüschenschmidt C, Chen J, Becker A, Riazanski V, Beck H
Department of Epileptology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Eur J Neurosci. 2006 Feb;23(3):675-85. doi: 10.1111/j.1460-9568.2006.04608.x.
A-type K+ channels are crucial determinants of neuronal firing. For example, reducing the amplitude of A-type currents (I(A)) increases seizure susceptibility. We have therefore examined the functional and molecular properties of I(A) in dentate granule neurons following pilocarpine-induced status epilepticus (SE). We found that the levels of various A-type channel subunit mRNAs are unaltered following SE. Furthermore, current density and biophysical properties of I(A) recorded in outside-out and cell-attached patches from dentate granule cells are not modified by SE. However, I(A) in both control and epileptic rats was powerfully regulated by the cellular redox state. I(A) was recorded in outside-out patches with the recording pipette containing either reduced (GSH) or oxidized (GSSG) glutathione. In both control and epileptic rats, the presence of GSSG caused a similar, marked acceleration of recovery from inactivation. Additionally, GSSG produced a small but significant reduction of I(A) amplitudes only in control rats. The inactivation time course of I(A) during depolarizing voltage steps was not modified by GSH or GSSG. Cell-attached recordings, in which the intracellular milieu is conserved, revealed a slow time course of recovery more comparable to that with GSH. In summary, epileptic activity does not produce chronic changes in the molecular and functional properties of the somatic I(A) of dentate granule cells. However, I(A) is powerfully modulated by oxidation in both control and epileptic rats. This finding suggests that the availability of I(A) may be strongly regulated by changes in the GSH/GSSG ratio occurring during prolonged seizure activity or hypoxia.
A 型钾通道是神经元放电的关键决定因素。例如，降低 A 型电流（I(A)）的幅度会增加癫痫易感性。因此，我们研究了毛果芸香碱诱导的癫痫持续状态（SE）后齿状颗粒神经元中 I(A)的功能和分子特性。我们发现，SE 后各种 A 型通道亚基 mRNA 的水平未发生改变。此外，从齿状颗粒细胞的外向膜片和细胞贴附膜片记录的 I(A)的电流密度和生物物理特性不受 SE 的影响。然而，对照大鼠和癫痫大鼠中的 I(A)均受到细胞氧化还原状态的强烈调节。使用含有还原型（GSH）或氧化型（GSSG）谷胱甘肽的记录电极在外向膜片中记录 I(A)。在对照大鼠和癫痫大鼠中，GSSG 的存在都会导致从失活状态恢复的速度显著加快，且情况相似。此外，GSSG 仅在对照大鼠中使 I(A)幅度出现小幅但显著的降低。去极化电压阶跃期间 I(A)的失活时间进程不受 GSH 或 GSSG 的影响。细胞贴附记录（其中细胞内环境得以保留）显示，恢复过程的时间进程较慢，更类似于使用 GSH 时的情况。总之，癫痫活动不会导致齿状颗粒细胞体细胞 I(A)的分子和功能特性发生慢性变化。然而，在对照大鼠和癫痫大鼠中，I(A)均受到氧化的强烈调节。这一发现表明，在长时间癫痫发作活动或缺氧期间发生的 GSH/GSSG 比值变化可能会强烈调节 I(A)的可用性。
