Federated Department of Biological Sciences, New Jersey Institute of Technology and Rutgers University, Newark, New Jersey 07102, USA.
J Neurophysiol. 2012 Jan;107(2):718-27. doi: 10.1152/jn.00622.2011. Epub 2011 Oct 12.
Neuronal identity depends on the regulated expression of numerous molecular components, especially ionic channels, which determine the electrical signature of a neuron. Such regulation depends on at least two key factors, activity itself and neuromodulatory input. Neuronal electrical activity can modify the expression of ionic currents in homeostatic or nonhomeostatic fashion. Neuromodulators typically modify activity by regulating the properties or expression levels of subsets of ionic channels. In the stomatogastric system of crustaceans, both types of regulation have been demonstrated. Furthermore, the regulation of the coordinated expression of ionic currents and the channels that carry these currents has been recently reported in diverse neuronal systems, with neuromodulators not only controlling the absolute levels of ionic current expression but also, over long periods of time, appearing to modify their correlated expression. We hypothesize that neuromodulators may regulate the correlated expression of ion channels at multiple levels and in a cell-type-dependent fashion. We report that in two identified neuronal types, three ionic currents are linearly correlated in a pairwise manner, suggesting their coexpression or direct interactions, under normal neuromodulatory conditions. In each cell, some currents remain correlated after neuromodulatory input is removed, whereas the correlations between the other pairs are either lost or altered. Interestingly, in each cell, a different suite of currents change their correlation. At the transcript level we observe distinct alterations in correlations between channel mRNA amounts, including one of the cell types lacking a correlation under normal neuromodulatory conditions and then gaining the correlation when neuromodulators are removed. Synaptic activity does not appear to contribute, with one possible exception, to the correlated expression of either ionic currents or of the transcripts that code for the respective channels. We conclude that neuromodulators regulate the correlated expression of ion channels at both the transcript and the protein levels.
神经元的身份取决于众多分子成分的调节表达，尤其是离子通道，它们决定了神经元的电信号特征。这种调节依赖于至少两个关键因素，即活动本身和神经调质输入。神经元的电活动可以以稳态或非稳态的方式改变离子电流的表达。神经调质通常通过调节离子通道亚群的特性或表达水平来调节活动。在甲壳类动物的口胃神经系统中，已经证明了这两种调节方式。此外，最近在不同的神经元系统中也报道了离子电流和携带这些电流的通道的协调表达的调节，神经调质不仅控制离子电流表达的绝对水平，而且在长时间内似乎还改变它们的相关表达。我们假设神经调质可能在多个水平上调节离子通道的相关表达，并以细胞类型依赖性的方式进行调节。我们报告说，在两种已鉴定的神经元类型中，三种离子电流以两两线性相关的方式表达，这表明它们在正常神经调质条件下共表达或直接相互作用。在每种细胞中，一些电流在神经调质输入去除后仍然相关，而其他对的相关性则丢失或改变。有趣的是，在每种细胞中，不同的电流套件改变它们的相关性。在转录水平上，我们观察到通道 mRNA 量之间相关性的明显变化，包括一种细胞类型在正常神经调质条件下缺乏相关性，然后在去除神经调质时获得相关性。突触活动似乎没有对离子电流或编码相应通道的转录本的相关表达做出贡献，除了一种可能的例外情况。我们得出结论，神经调质在转录和蛋白水平上调节离子通道的相关表达。
