Modulation of Two Transient Potassium Currents in Mouse Hippocampal Neurons

神经元的个性是由存在于神经元膜上的功能性离子通道的特殊补体决定的。不同的神经元表达不同数量的选择钠、钙、钾和氯离子的通道，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。实验将在培养的胚胎小鼠海马神经元上进行，这是研究早期神经发育的标准准备。先前已经观察到，两种不同形式的瞬态钾电流（称为a电流和d电流）在神经元中的表达依赖于与非神经元胶质细胞的接触。由于A电流和d电流参与神经元电生成，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。为了理解这一过程是如何发生的，必须明确A-和d -电流通道之间的精确分子关系。在目前的实验中，在单通道水平上的门控和渗透行为的差异将被检查。未来的实验将集中在基因表达和翻译后修饰的问题上，这些问题可能会建立A-和d -电流下离子通道之间的差异。

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.