Transcriptional Regulation of Potassium Current

钾电流的转录调节

• 批准号: 9603978
• 负责人: Nicholas Spitzer
• 金额: $ 15万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-15 至 2002-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9603978&HistoricalAwards=false
• 关键词: Transcriptional; Regulation; Potassium; Current

PI: Spitzer IBN: 9603978 Dr. Spitzer will analyze the molecular mechanisms that underlie expression of potassium current in embryonic spinal nerve cell. Nerve cells transmit information with electrical signals, and acquire the ability to generate these signals called action potentials at very early stages of differentiation. Initially, these action potentials allow the entry of substantial amounts of calcium ions. Dr. Spitzer has shown that this calcium influx generates important signals that regulate several aspects of the development of nerve cells. However, since this amount of calcium entry is toxic to mature nerve cells, the neurons must dramatically reduce the amount of calcium entry as they mature. In earlier work Dr. Spitzer showed that the reduction of calcium influx is the result of an increase in potassium current that flows out of the nerve cells through protein pores, called potassium channels, opposing the calcium influx. In the work supported by this grant he will determine the basis of the developmental increase in this potassium current. Preliminary results suggest that expression of a particular gene, known as Kv2.2, which encodes the protein of which potassium channels are composed, may be responsible for the increase in this potassium current. Dr. Spitzer will use antisense DNA sequences to suppress the synthesis of the protein in nerve cells isolated and growing in culture. He will take advantage of the availability of a toxin, hanatoxin, that is a specific blocker of these channels, to check the success of these experiments. If the antisense treatment suppresses expression of the Kv2.2 protein, the toxin will no longer affect the potassium current. The results from the project will provide new knowledge about the regulation of excitability in the spinal cord. The fact that the central nervous system of young vertebrates is especially vulnerable to epileptic seizure activity may be partly due to the calcium influx that is part of the early signaling mac hinery. In the future it may be possible to suppress this calcium influx selectively by regulating the expression of particular potassium channel genes.

PI：Spitzer IBN：9603978 Spitzer博士将分析钾脊髓神经细胞中钾电流表达的分子机制。 神经细胞用电信号传输信息，并获得在分化的早期阶段生成这些称为动作电位的信号的能力。 最初，这些动作电位允许进入大量钙离子。 Spitzer博士表明，这种钙涌入会产生重要的信号，以调节神经细胞发展的几个方面。 但是，由于这种量的钙进入对成熟的神经细胞有毒，因此神经元必须在成熟时大大减少钙进入量。 Spitzer博士在较早的工作中表明，钙涌入的减少是钾电流增加的结果，该钾电流通过蛋白质孔（称为钾通道）从神经细胞中流出，与钙涌入相反。 在这笔赠款支持的工作中，他将确定该钾电流发育增加的基础。 初步结果表明，特定基因的表达（称为kv2.2）编码钾通道的蛋白质的编码可能是该钾电流增加的原因。 Spitzer博士将使用反义DNA序列来抑制在培养中分离和生长的神经细胞中蛋白质的合成。 他将利用这些通道的特定阻滞剂的毒素Hanatoxin的可用性来检查这些实验的成功。 如果反义治疗抑制Kv2.2蛋白的表达，则毒素将不再影响钾电流。 该项目的结果将提供有关调节脊髓兴奋性的新知识。 年轻脊椎动物的中枢神经系统尤其容易受到癫痫发作活性的事实可能部分是由于钙涌入是早期信号Mac Hinery的一部分。 将来，可以通过调节特定钾通道基因的表达来选择性地抑制这种钙流入。