Hippocalcin gates the calcium activation of the slow afterhyperpolarization in hippocampal pyramidal cells
Hippocalcin gates the calcium activation of the slow afterhyperpolarization in hippocampal pyramidal cells
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DOI：
10.1016/j.neuron.2007.01.011
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发表时间：
2007-02-15
期刊：
影响因子：
16.2
通讯作者：
Nicoll, Roger A.
中科院分区：
文献类型：
--
作者：
Tzingounis, Anastassios V.;Kobayashi, Masaaki;Nicoll, Roger A.
在大脑中，一系列动作电位后的钙内流激活钾通道，介导缓慢的后超极化电流（I-sAHP）。钙离子内流和钾通道激活之间的关键步骤仍然未知。在这里，我们报告，钙和sAHP通道之间的关键中间体是可扩散的钙传感器calcin。足以激活野生型小鼠中IsAHP的短暂去极化不会引起Ekcalcin敲除小鼠中的I-sAHP。在培养的海马神经元中引入N-calcin导致明显的IsAHP，而表达N-calcin突变体的神经元缺乏N-末端肉豆蔻酰化表现出小的I-sAHP，这与未感染的神经元中记录的类似。这意味着钙调素必须与质膜结合以介导其作用。这些发现支持一个模型，其中的钙传感器的sAHP通道是不preassociated与通道复杂。
In the brain, calcium influx following a train of action potentials activates potassium channels that mediate a slow afterhyperpolarization current (I-sAHP). The key steps between calcium influx and potassium channel activation remain unknown. Here we report that the key intermediate between calcium and the sAHP channels is the diffusible calcium sensor hippocalcin. Brief depolarizations sufficient to activate the IsAHP in wild-type mice do not elicit the I-sAHP in hippocalcin knockout mice. Introduction of hippocalcin in cultured hippocampal neurons leads to a pronounced IsAHP, while neurons expressing a hippocalcin mutant lacking N-terminal myristoylation exhibit a small I-sAHP that is similar to that recorded in uninfected neurons. This implies that hippocalcin must bind to the plasma membrane to mediate its effects. These findings support a model in which the calcium sensor for the sAHP channels is not preassociated with the channel complex.