RGD Reference Report - Modulation of the cardiac sodium channel Nav1.5 by fibroblast growth factor homologous factor 1B. - Rat Genome Database

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

Authors: Liu, CJ  Dib-Hajj, SD  Renganathan, M  Cummins, TR  Waxman, SG 
Citation: Liu CJ, etal., J Biol Chem. 2003 Jan 10;278(2):1029-36. Epub 2002 Oct 24.
RGD ID: 6484231
Pubmed: PMID:12401812   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M207074200   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Molecular Function

  

Objects Annotated

Genes (Rattus norvegicus)
Fgf12  (fibroblast growth factor 12)
Scn11a  (sodium voltage-gated channel alpha subunit 11)
Scn5a  (sodium voltage-gated channel alpha subunit 5)


Additional Information