INFORMATION PROCESSING BY CALCIUM-ACTIVATED K+ CHANNELS

离子通道是神经系统中所有电信号的基础， 神经信息的基本计算单位也是如此 正在处理。为了了解学习和记忆在细胞和 分子水平，聚合为调制的复杂分子网络 离子通道必须被阐明。在本研究中，钙离子被激活 钾(KCA)通道将作为一个模型系统来研究如何 离子通道的门控是通过以下组合作用来修改的 多种蛋白激酶、钙离子和电压。KCA渠道具有特殊性 与可塑性机制有关，因为它们提供了一种 神经元内钙离子浓度及其膜电压。氨基 克隆的KCA通道的酸序列显示了丰富的复合体潜力 监管；有多个关于ATP的共识站点，至少有五个 不同类型的蛋白激酶。三个具体目标将是 利用在哺乳动物中表达的果蝇和人KCA通道进行追踪 细胞系和非洲爪哇的卵母细胞有：1)要表征该通道的 电压和钙依赖2)以确定个体的影响 蛋白激酶在通道门控中的作用 作用于单一通道的多个蛋白激酶。五人小组 将单独和以不同的方式对通道应用Kinase 组合和由此产生的浇注动力学模式将是 以膜片钳记录为特征。因此，虽然单个蛋白质 激酶可能对通道有特殊的影响，新的门控特性 可能出现在多个激酶的组合作用中。在……里面 此外，转移的磷酸基团的顺序、数目和位置 可能对通道选通有特定的影响。就这样， 单通道分子可以整合甚至存储新陈代谢 信息。

Ion channels underlie all electrical signaling in the nervous system and so are the fundamental computational units of neural information processing. To understand learning and memory at the cellular and molecular level, the complex molecular networks that converge to modulate ion channels must be elucidated. In this study, the Ca2+-activated potassium (KCa) channel will be used as a model system to examine how the gating of ion channels is modified by the combinatorial action of multiple protein kinases, Ca2+, and voltage. KCa channels are of special relevance to mechanisms of plasticity as they provide a link between a neurons internal Ca2+ concentration and its membrane voltage. The amino acid sequences of cloned KCa channels reveal a rich potential for complex regulation; there are multiple consensus sites for ATP and at least five different types of protein kinase. The three specific aims that will be pursued using Drosophila and human KCa channels expressed in mammalian cell lines and Xenopus oocytes are: 1) to characterize the channel's voltage- and calcium-dependence 2) to identify the effects of individual protein kinases on channel gating and 3) to describe the interaction of multiple protein kinases acting on a single channel. A panel of five kinases will be applied to the channel individually and in various combinations and the resultant patterns of gating kinetics will be characterized using patch-clamp recording. Thus, while a single protein kinase may have a particular effect on the channel, new gating properties may emerge from the combinatorial action of multiple kinases. In addition, the order, number, and position of phosphate groups transferred by the kinases may have specific effects on channel gating. In this way, a single channel molecule could integrate and even store metabolic information.