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Investigation of the Association of SCN1B with Cardiac Junctional and Ion Channel Proteins at the Intercalated Disc
Author(s) -
Gatt Jessica Lane,
Isom Lori L.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1037.1
Subject(s) - intercalated disc , connexin , ion channel , biology , microbiology and biotechnology , gap junction , genetics , receptor , intracellular
Voltage‐gated Na + channels (VGSCs), located in cardiac intercalated discs, are heterotrimeric molecules containing a central, pore‐forming α subunit and two multifunctional β subunits, associated with multiple proteins to ensure rapid, synchronous electrical transduction of action potentials through cardiac myocytes. Mutations in genes encoding VGSC α and β subunits can lead to cardiac arrhythmias, including Long‐QT and Brugada Syndromes. We propose that VGSC β1, encoded by SCN1B , plays an integral role in forming multimolecular signaling complexes in heart. Our aim was to use the SCN1B null mouse model to investigatec interactions of Na v 1.5 with junctional and ion channel proteins that are dependent on β1. This information will provide insight into how SCN1B mutations lead to cardiac arrhythmia. Using co‐immunoprecipitation, we investigated the association of Na v 1.5 with K v 4.3, N‐cadherin, and connexin‐43, in solubilized SCN1B null and wildtype heart membranes. Previous studies showed that β1 associates with Na v 1.5, N‐cadherin, and connexin‐43 in transfected cells. The present in vivo results suggest that Na v 1.5 and K v 4.3 form a macromolecular complex in wildtype heart. Na v 1.5 and N‐cadherin associate in wildtype but not SCN1B null heart, suggesting that β1 is critical for Na v 1.5‐N‐cadherin interactions. Na v 1.5 and Cx‐43 remain associated in the SCN1B null heart, suggesting this interaction does not depend on β1. Our results suggest that VGSC β1 is an integral molecular adaptor, organizing and linking Na v 1.5 complexes to key junctional and ion channel proteins in the intercalated disc.