Referenced in: none

Automatically associated channels: Kv7.1 , Nav1.5

Title: Modulation of the cardiac sodium channel Nav1.5 by fibroblast growth factor homologous factor 1B.

Authors: Chuan-ju Liu, Sulayman D Dib-Hajj, Muthukrishnan Renganathan, Theodore R Cummins, Stephen G Waxman

Journal, date & volume: J. Biol. Chem., 2003 Jan 10 , 278, 1029-36

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12401812

Abstract
We have previously shown that fibroblast growth factor homologous factor 1B (FHF1B), a cytosolic member of the fibroblast growth factor family, associates with the sensory neuron-specific channel Na(v)1.9 but not with the other sodium channels present in adult rat dorsal root ganglia neurons. We show in this study that FHF1B binds to the C terminus of the cardiac voltage-gated sodium channel Na(v)1.5 and modulates the properties of the channel. The N-terminal 41 amino acid residues of FHF1B are essential for binding to Na(v)1.5, and the conserved acidic rich domain (amino acids 1773-1832) in the C terminus of Na(v)1.5 is sufficient for association with this factor. Binding of the growth factor to recombinant wild type human Na(v)1.5 in human embryonic kidney 293 cells produces a significant hyperpolarizing shift in the voltage dependence of channel inactivation. An aspartic acid to glycine substitution at position 1790 of the channel, which underlies one of the LQT-3 phenotypes of cardiac arrythmias, abolishes the interaction of the Na(v)1.5 channel with FHF1B. This is the first report showing that interaction with a growth factor can modulate properties of a voltage-gated sodium channel.