We have recently cloned a novel Ca channel alpha1 subunit which we have named alpha1c. The transcript for this channel is widely distributed in the nervous system. However, expression of alpha1c 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 alpha1c 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 alpha1c to be used for examining the distribution of the protein and its expression. 2) Expression of different splice variants of alpha1c in combination with different ancillary subunits in order to provide information on how alpha1c based Ca currents may normal appear. 3) Investigations of whether alpha1c currents can be regulated by diverse second messengers and receptors. 4) Removal of alpha1c 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 alpha1c. These experiments will utilize a combination of biophysical and molecular biological paradigms. It is hope that these studies will provide us with important information about the functions of this novel neuronal Ca channel.
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