Grant: Operating Grant

Calcium plays a number of highly important roles in human physiology. In the brain, calcium entering into nerve cells controls nerve to nerve communication and triggers a variety of intracellular signaling processes. At the same time, too much calcium is toxic, and hence, the amount of calcium entering brain cells must be precisely controlled. One key player in the regulation of calcium entry is a family of proteins termed "calcium channels". Several differenct types of calcium channels have been identified in mammalian brain, each with a unique role in the function of the nervous system. T-type calcium channels, the focus of this proposal, contribute to the regulation of cell growth, and how effectively nerve impulses are conducted. Genetic abnormalities in these channels have been linked to absence epilepsy in children, and they are considered important pharmacological targets in the treatment of seizures. In this application, we propose to investigate in detail how the function of these channels is controlled at the molecular level, and how mutations linked to childhood epilepsy affect nerve cell function. In addition, we will examine how channel function can affect other types of ion channels. This will be accomplished through a combination of state of the art molecular and neurophysiological techniques. We anticipate that our findings will help guide new therapeutic strategies towards treatment of disorders linked to these channels.