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

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

Research output: Contribution to journalArticle

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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 Nav1.9 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 Nav1.5 and modulates the properties of the channel. The N-terminal 41 amino acid residues of FHF1B are essential for binding to Nav1.5, and the conserved acidic rich domain (amino acids 1773-1832) in the C terminus of Nav1.5 is sufficient for association with this factor. Binding of the growth factor to recombinant wild type human Nav1.5 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 Nav1.5 channel with FHF1B. This is the first report showing that interaction with a growth factor can modulate properties of a voltage-gated sodium channel.

Original languageEnglish (US)
Pages (from-to)1029-1036
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number2
DOIs
StatePublished - Jan 10 2003
Externally publishedYes

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Fibroblast Growth Factors
Sodium Channels
NAV1.5 Voltage-Gated Sodium Channel
Neurons
Intercellular Signaling Peptides and Proteins
Modulation
Voltage-Gated Sodium Channels
Amino Acids
Spinal Ganglia
Sensory Receptor Cells
Aspartic Acid
Glycine
Rats
Cardiac Arrhythmias
Substitution reactions
Association reactions
Phenotype
Kidney
Electric potential

ASJC Scopus subject areas

  • Biochemistry

Cite this

Modulation of the cardiac sodium channel Nav1.5 by fibroblast growth factor homologous factor 1B. / Liu, Chuan ju; Dib-Hajj, Sulayman D.; Renganathan, Muthukrishnan; Cummins, Theodore; Waxman, Stephen G.

In: Journal of Biological Chemistry, Vol. 278, No. 2, 10.01.2003, p. 1029-1036.

Research output: Contribution to journalArticle

Liu, Chuan ju ; Dib-Hajj, Sulayman D. ; Renganathan, Muthukrishnan ; Cummins, Theodore ; Waxman, Stephen G. / Modulation of the cardiac sodium channel Nav1.5 by fibroblast growth factor homologous factor 1B. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 2. pp. 1029-1036.
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