Control of electrical activity in central neurons by modulating the gating of small conductance Ca2+-activated K+ channels
Control of electrical activity in central neurons by modulating the gating of small conductance Ca2+-activated K+ channels
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DOI：
10.1074/jbc.m010001200
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发表时间：
2001-03-30
影响因子：
4.8
通讯作者：
Fakler, B
中科院分区：
文献类型：
--
作者：
Pedarzani, P;Mosbacher, J;Fakler, B
在大多数中枢神经元中，动作电位之后是控制放电模式和兴奋性的后超极化（AHP）。克隆的SK通道是SK α-亚基和钙调素的异聚体复合物，通道被Ca ~（2+）结合到钙调素上引起构象变化而激活，导致通道开放，通道失活是Ca ~（2+）Rom钙调素解离引起的相反过程。应用EBIO克隆SK通道转移到较低的纳摩尔范围内的Ca 2+浓度-反应关系，并减缓通道失活几乎10倍。在海马CA 1区神经元，EBIO增加了中，慢AHP，强烈降低电活动。此外，EBIO抑制低Mg ~（2+）诱导的培养皮层神经元的过度兴奋。这些结果强调了SK通道对塑造中枢神经元电反应模式的重要性，并表明调节SK通道门控是控制中枢神经系统兴奋性的有效机制。
In most central neurons, action potentials are followed by an afterhyperpolarization (AHP) that controls firing pattern and excitability, The medium and slow components of the AHP have been ascribed to the activation of small conductance Ca2+-activated potassium (SK) channels. Cloned SK channels are heteromeric complexes of SK alpha -subunits and calmodulin, The channels are activated by Ca2+ binding to calmodulin that induces conformational changes resulting in channel opening, and channel deactivation is the reverse process brought about by dissociation of Ca2+ Rom calmodulin, Here we show that SK channel gating is effectively modulated by 1-ethyl-2-benzimidazolinone (EBIO). Application of EBIO to cloned SK channels shifts the Ca2+ concentration-response relation into the lower nanomolar range and slows channel deactivation by almost 10-fold. In hippocampal CA1 neurons, EBIO increased both the medium and slow AHP, strongly reducing electrical activity. Moreover, EBIO suppressed the hyperexcitability induced by low Mg2+ in cultured cortical neurons. These results underscore the importance of SK channels for shaping the electrical response patterns of central neurons and suggest that modulating SK channel gating is a potent mechanism for controlling excitability in the central nervous system.