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 处理.为了理解细胞和大脑中的学习和记忆， 在分子水平上，复杂的分子网络汇聚在一起， 必须阐明离子通道。在这项研究中，Ca 2+激活的 钾（KCa）通道将被用作一个模型系统，以研究如何 离子通道的门控通过以下的组合作用来改变： 多种蛋白激酶、Ca 2+和电压。KCa通道具有特殊的 与可塑性机制的相关性，因为它们提供了 神经元内Ca ~（2+）浓度和膜电压。氨基 克隆的KCa通道的酸序列揭示了复合物的丰富潜力。 调节; ATP有多个共识位点， 不同类型的蛋白激酶。三个具体目标将是 使用在哺乳动物中表达的果蝇和人KCa通道进行研究 细胞系和非洲爪蟾卵母细胞是：1）表征通道的 电压依赖性和钙依赖性2）以确定个体 蛋白激酶对通道门控的影响，以及3）描述 多个蛋白激酶作用于单个通道。五人小组 激酶将被单独地和以各种方式应用于通道。 组合和门控动力学的所得模式将是 其特征在于使用膜片钳记录。因此，虽然一种蛋白质 激酶可能对通道有特殊的影响，新的门控特性 可能来自多种激酶的组合作用。在 此外，转移的磷酸基团的顺序、数量和位置 可能对通道门控有特定的影响。通过这种方式， 单个通道分子可以整合甚至储存代谢产物 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.