NOVEL NEURONAL CALCIUM CHANNEL

我们最近克隆了一个新的钙通道α1亚基，我们拥有 名字叫字母1e。这个频道的成绩单广泛分布在 神经系统。然而，字母1e的表达会产生钙电流 在几个方面都是神秘的。生物物理学和 电流的药理学特征与那些 这是普遍报道的--但也有一些例外。我们现在 希望进一步调查情况，以期建立 正常细胞中α-基电流的特征及其意义 生理功能。为了做到这一点，我们将采取不同的 该方法将包括以下类型的实验。1) 抗人α1e抗体的制备及检测 蛋白质的分布及其表达。2)表达不同 α1e的剪接变体与不同的辅助成分相结合 亚基，以便提供关于基于α1e的钙电流的信息 可能会正常出现。3)研究α电流是否可以 受不同的第二信使和受体调节。4)删除 从正常存在的细胞中转录出来的字母1e和 检查这对细胞功能的影响。5)考试 不同形式的字母的分布情况。这些实验 将利用生物物理学和分子生物学的结合 范例。希望这些研究将为我们提供重要的 关于这种新的神经元钙通道功能的信息。

We have recently cloned a novel Ca channel alpha1 subunit which we have named alpha1e. The transcript for this channel is widely distributed in the nervous system. However, expression of alpha1e produces Ca currents that are mysterious in several respects. The biophysical and pharmacological profile of the currents are not really similar to those that have generally been reported - with a number of exceptions. We now wish to investigate the situation further with a view to establishing the characteristics of alpha1e based currents in normal cells and their physiological functions. In order to do this we shall take a varied approach which will include the following types of experiments. 1) Preparation of antibodies against alpha1e to be used for examining the distribution of the protein and its expression. 2) Expression of different splice variants of alpha1e in combination with different ancillary subunits in order to provide information on how alpha1e based Ca currents may normally appear. 3) Investigations of whether alpha1e currents can be regulated by diverse second messengers and receptors. 4) Removal of alpha1e transcripts from cells in which they normally occur and examination of the consequences of this for cell function. 5) Examination of the distribution of the different forms of alpha1e. These experiments will utilize a combination of biophysical and molecular biological paradigms. It is hoped that these studies will provide us with important information about the functions of this novel neuronal Ca channel.