Abstract 2279 Phosphorylation control of Kv7.2 structure and interactions in response to GPCR signals

Voltage-gated potassium channels of subfamily 7 (Kv7) are important regulators of cellular membrane potential. The Kv7.2 subunit is one of 5 different subunits encoded by the KCNQ genes that forms heteromeric tetramers with Kv7.3 and Kv7.5 subunits in neurons. Dysfunction of these subunits causes neonatal epilepsy and developmental disorders, with over 80 different pathological mutations reported on the KCNQ2 gene. Many of these mutations lie within the B helix domain of the intracellular C termini of Kv7.2 that bind to the three Gαq11 protein coupled receptor (GPCR) signaling cofactors: Ca2+-regulated calmodulin (CaM), phosphatidylinositol 4,5-bisphosphate (PIP2) and protein kinase C (PKC).