The BK-mediated fAHP is modulated by learning a hippocampus-dependent task
The BK-mediated fAHP is modulated by learning a hippocampus-dependent task
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DOI：
10.1073/pnas.0805855105
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发表时间：
2008-09-30
影响因子：
11.1
通讯作者：
Disterhoft, John F.
中科院分区：
文献类型：
--
作者：
Matthews, Elizabeth A.;Weible, Aldis P.;Disterhoft, John F.
内在兴奋性是细胞的一种可塑性，沿着突触的变化，可以通过学习来调节。动作电位（AP）的高度、宽度和频率是依赖于树突、体细胞和轴突膜中Na+、Ca2+和K（+）通道激活的内在控制特性。AP后的快速超极化（fAHP）部分决定了AP的半宽和持续时间，从而决定了去极化期间的Ca2+内流。在CA1海马锥体细胞中，fAHP由电压和Ca 2+依赖性BK通道携带。除了调节AP的持续时间外，BK介导的钾电流还控制AP产生的频率，以响应去极化输入。这些事实使BK介导的作用不仅调节神经元内的即时通讯，而且控制神经元中的长期Ca2+依赖性变化，如激酶激活、基因转录和突触可塑性。我们研究了BK介导的fAHP是如何在学习轨迹眨眼条件反射后改变海马神经元的。通过使用电流钳方法，发现在来自条件化动物的细胞中fAHP减少并且AP持续时间增加。此外，在体外和体内测量的放电频率表明，BK通道阻滞剂增加诱发（体外）和自发（体内）放电频率的CA1神经元，暗示BK通道的内在兴奋性的控制。这些数据表明，BK介导的fAHP的减少是已知伴随海马依赖性学习的神经元兴奋性总体增加的重要部分。
Intrinsic excitability is a plastic property of cells that, along with synaptic changes, can be modulated by learning. Action potential (AP) height, width, and frequency are intrinsically controlled properties which rely on the activation of Na+, Ca2+, and K (+) channels in the dendritic, somatic, and axonal membranes. The fast after hyperpolarization (fAHP) after an AP is partially responsible for determining the half-width and duration of the AP and thus Ca2+ influx during the depolarization. In CA1 hippocampal pyramidal cells, the fAHP is carried by the voltage- and Ca2+-dependent BK channel. In addition to modulating the duration of the AP, the BK-mediated potassium current exerts control over the frequency of AP generation in response to a depolarizing input. These facts position BK-mediated effects to not only modulate immediate intraneuronal communication, but also to control longer-term Ca2+-dependent changes in the neuron, such as kinase activation, gene transcription, and synaptic plasticity. We examined how the BK-mediated fAHP was altered in hippocampal neurons after learning trace eyeblink conditioning. By using current clamp methods, it was found that the fAHP is reduced and the AP duration is increased in cells from conditioned animals. Additionally, in vitro and in vivo measures of firing frequency show that BK-channel blockade increases both evoked (in vitro) and spontaneous (in vivo) firing frequency of CA1 neurons, implicating the BK channel in the control of intrinsic excitability. These data indicate that the reduction of the BK-mediated fAHP is an essential part of the total increase of neuronal excitability known to accompany hippocampus-dependent learning.