小电导Ca2+激活K+(SK)通道,在整个中枢神经系统中表达,由SK1、SK2和SK3亚基组成,组装为同源四聚体或异源四聚体蛋白。表达的SK通道通过介导超极化后的中等成分来调节神经元的兴奋性。突触SK通道塑造兴奋性突触后电位和突触可塑性。这种SK介导的对神经元兴奋性和活动依赖性突触强度的影响可能是SK通道对记忆编码的调节作用的基础。融合的证据表明,使用SK通道阻滞剂可以促进几种形式的长期记忆,阿帕明,并因使用pan-SK通道激活剂而受损,1-EBIO,或通过SK2亚基的过表达。树突状SK2亚基的选择性敲低促进记忆的程度与全身性阿帕明后观察到的程度相似。SK1亚基与SK2共组装;然而SK1的功能意义尚未明确定义。这里,我们检查了GW542573X的效果,一种激活含有SK通道的SK1的药物,以及SK2/3,对雄性C57BL/6J小鼠的几种形式的长期记忆。我们的结果表明,培训前,但不是培训后,在训练后24小时测试小鼠的系统性GW542573X受损的对象记忆和恐惧记忆。训练前直接双侧输注GW542573X进入海马受损对象的CA1记忆编码。这些数据表明全身性GW542573X损害长期记忆。这些结果增加了越来越多的证据表明SK2亚单位-,和SK1亚单位-,含有SK通道可以调节编码海马依赖性记忆所必需的行为触发的突触可塑性。
Small conductance Ca2+-activated K+ (SK) channels, expressed throughout the CNS, are comprised of SK1, SK2 and SK3 subunits, assembled as homotetrameric or heterotetrameric proteins. SK channels expressed somatically modulate the excitability of neurons by mediating the medium component of the afterhyperpolarization. Synaptic SK channels shape excitatory postsynaptic potentials and synaptic plasticity. Such SK-mediated effects on neuronal excitability and activity-dependent synaptic strength likely underlie the modulatory influence of SK channels on memory encoding. Converging evidence indicates that several forms of long-term memory are facilitated by administration of the SK channel blocker, apamin, and impaired by administration of the pan-SK channel activator, 1-EBIO, or by overexpression of the SK2 subunit. The selective knockdown of dendritic SK2 subunits facilitates memory to a similar extent as that observed after systemic apamin. SK1 subunits co-assemble with SK2; yet the functional significance of SK1 has not been clearly defined. Here, we examined the effects of GW542573X, a drug that activates SK1 containing SK channels, as well as SK2/3, on several forms of long-term memory in male C57BL/6J mice. Our results indicate that pre-training, but not post-training, systemic GW542573X impaired object memory and fear memory in mice tested 24 h after training. Pre-training direct bilateral infusion of GW542573X into the CA1 of hippocampus impaired object memory encoding. These data suggest that systemic GW542573X impairs long-term memory. These results add to growing evidence that SK2 subunit-, and SK1 subunit-, containing SK channels can regulate behaviorally triggered synaptic plasticity necessary for encoding hippocampal-dependent memory.