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Physical Mechanisms And Biological Consequences Of Voltage-Gated Sodium Channel Modulation By Fhf Proteins, Yue Liu
Dissertations, Theses, and Capstone Projects
Purpose: FHFs are cytosolic proteins that bind to voltage-gated sodium channels (NaVs) and modulate their functions to control membrane excitability. FHFs raise the voltage dependence of NaV fast inactivation to promote excitability, while A isoforms FHF (A-FHFs) also capture open sodium channels into a long-term inactivated (LTI) state to limit excitability. My research has addressed how FHFs balance membrane excitability as it relates to normal and pathological brain functions. Part of this work stemmed from the discovery of a missense FHF1 mutation in patients with severe early onset epilepsy. Methods and Results: Wild-type FHF1A and FHF1B were …