Grant: Project Grant

Cells in the nervous system rapidly propagate signals by generating 'action potentials', brief changes in the voltage across the cell membrane. Action potentials are generated by the opening and closing of ion channel proteins that conduct electrical currents. Defects in the function of ion channel proteins can lead to a variety of neurological diseases including epilepsy and movement disorders. Our research has uncovered an interesting mechanism that dramatically regulates a specific ion channel protein in response to a cellular property called the 'redox potential'. The cellular redox potential is closely tied to energy generation and metabolism, and so we suspect that this regulatory feature provides a previously unrecognized link between electrical signaling and metabolism. The proposed research will reveal the specific molecules involved in this regulatory mechanism, and will also investigate the outcome of disrupting this signaling pathway in an engineered mouse model. Overall, this project will pave the way for a deeper understanding of how the function of electrical signaling proteins in the brain might be altered in neurological diseases and targeted for their treatment.