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Modulation of voltage‐gated potassium channels by sodium channel SCN1b subunits
Author(s) -
Nguyen Hai Minh,
Calhoun Jeffrey Dennis,
Goldin Alan L.,
Isom Lori L.,
Chandy George K.
Publication year - 2012
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.26.1_supplement.901.4
Subject(s) - sodium channel , xenopus , potassium channel , voltage gated potassium channel , subfamily , voltage gated ion channel , ion channel , biology , biophysics , chemistry , sodium , genetics , receptor , organic chemistry , gene
Although voltage‐gated Nav1 sodium channels and Kv1 potassium channels are both known for their tandem function in action potential firing and have ubiquitous tissue expressions, to date, no functional association between members of the Nav1.x channel family and the Kv1 channel family have been reported. Here we report that SCN1b modulates the Kv1‐subfamily of K + channels, each in a unique fashion, when co‐expressed in Xenopus oocytes or mammalian cells (Table). Biochemical experiments show that SCN1b is physically coupled to Kv1 channels. Using chimeras of SCN1b and the myelin Po protein, we demonstrate that the external domain of SCN1b is essential for channel modulation. Two known epilepsy‐causing mutations in the Ig‐domain of SCN1b, R85C and C121W, disrupt Kv1 channel‐modulation. Thus, sodium channel beta subunits may regulate action potential firing and propagation in normal and diseased conditions by modulating the function of both Nav and Kv channels.