Modulation of Two Transient Potassium Currents in Mouse Hippocampal Neurons

小鼠海马神经元中两种瞬态钾电流的调节

• 批准号: 9121751
• 负责人: Michael Barish
• 金额: $ 2万
• 依托单位: Beckman Research Institute City of Hope
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-15 至 1993-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9121751&HistoricalAwards=false
• 关键词: Modulation; Two; Transient; Potassium; Currents

The individuality of neurons is determined by the particular complement of functional ion channels present in the neuronal membrane. Different neurons express varying numbers of channels selective for sodium, calcium, potassium and chloride ions, and as a consequence have specific patterns of responses to incoming excitatory and inhibitory stimuli. In order to understand how the individuality of neurons is established, a class of potassium currents whose activity influences both the waveform of single action potentials and the pattern of repetitive action potentials will be studied. Experiments will be performed on cultured embryonic mouse hippocampal neurons, a standard preparation for study of early neural development. It has been previously observed that the expression in neurons of two variant forms of transient potassium currents, termed A-current and D-current, is dependent on contact with non-neuronal glial cells. Since A- and D-currents are involved in neuronal electrogenesis, these observations raise the possibility that glial cells modulate neuronal activity by influencing channel expression. To understand how this process might occur, the precise molecular relationship between A- and D-current channels should be clarified. In the present experiments differences in gating and permeation behavior at the single channel level will be examined. Future experiments will focus on issues of gene expression and post-translational modification that may establish the differences between the ion channels underlying A- and D-currents.

神经元的个体性是由神经细胞膜中存在的功能离子通道的特殊补充决定的。不同的神经元表达不同数量的对钠、钙、钾和氯离子有选择性的通道，因此对传入的兴奋性和抑制性刺激有特定的反应模式。为了了解神经元的个体性是如何建立的，我们将研究一类钾电流，它的活动既影响单个动作电位的波形，也影响重复动作电位的模式。实验将在培养的小鼠胚胎海马神经元上进行，这是研究早期神经发育的标准准备。以前已经观察到，神经元中两种不同形式的瞬时钾电流，称为A-电流和D-电流，其表达依赖于与非神经元胶质细胞的接触。由于A-和D-电流参与神经元的电发生，这些观察结果提出了神经胶质细胞通过影响通道表达来调节神经元活动的可能性。为了了解这一过程是如何发生的，A-电流和D-电流通道之间的精确分子关系应该得到澄清。在本实验中，将考察在单通道水平上的栅极和渗透行为的差异。未来的实验将集中在基因表达和翻译后修饰的问题上，这可能会确定A-电流和D-电流背后的离子通道之间的差异。