Regulation of Kv1.2 Potassium Channel Trafficking by Adenylate Cyclase: Mechanisms

Specific Aims By modulating action potential firing patterns and neurotransmitter release dynamics throughout the brain, the Shaker family voltage-gated potassium channel Kv1.2 is a critical regulator of neurophysiology. However, mechanisms by which neuronal Kv1.2 may be regulated are poorly understood. In heterologous expression systems, Kv1.2 is regulated by endocytic trafficking, and both adenylate cyclase (AC) and protein kinase A (PKA) influence that trafficking. The long term goal of this research is to determine whether AC/PKA dependent modulation of Kv1.2 trafficking is a novel mechanism regulating synaptic function. However, there are major hurdles towards testing that hypothesis: there is no evidence for neuronal Kv1.2 trafficking, endocytic proteins by which AC/PKA regulates Kv1.2 trafficking are unclear, and resolving spatiotemporal regulation of Kv1.2 trafficking is limited by the absence of non-destructive assays. Therefore, three aims are proposed: