IBN-9723250 PI: Schafer Voltage-gated calcium channels control the entry of calcium into neurons and muscle cells. As such they serve as key regulators of calcium-dependent processes such as muscle contraction, communication between neurons, and learning. The importance of voltage-gated calcium channels for nervous system function is underscored by the fact that several devastating genetic and autoimmune diseases, such as sporadic ALS, are caused by calcium channel defects. Yet despite the scientific and medical importance of these channels, several key questions about calcium channel biology remain unanswered. For example, the functions of the individual proteins that make up the channel are not completely understood, nor is it clear how these proteins are assembled to make a working channel. The mechanisms through which calcium channel activity is regulated also remain largely uncharacterized. In the proposed studies, these questions will be addressed in the roundworm Caenorhabditis elegans using a combination of genetic and biochemical approaches. C. elegans has a simple and anatomically well characterized nervous system that is highly amenable to genetic analysis. Mutants defective in the genes for the calcium channel subunits will be used to define the roles of these proteins in the assembly, localization, and functional activity of the calcium channel. Mutant worms will also be identified that will define new genes required for regulation of calcium channel activity. These studies should provide important insights into general mechanisms for the regulation of voltage-gated calcium channels in neurons.
