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.
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