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BDNF receptor TrkB modulates voltage‐gated K+ (Kv) 1.5 channel protein expression
Author(s) -
Makar Tapas K,
Nooli Nishank P,
Nimmagadda Vamshi,
Patibandla Gopi Krishna,
Chakravarty Rumon,
Judge Susan I. V,
Maiti Atanu,
Bever Christopher T
Publication year - 2011
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.25.1_supplement.561.6
Brain derived neurotrophic factor (BDNF) regulates growth and regeneration. It can also modulate the activity of voltage gated ion channels. It has been reported that activation of BDNF receptor TrkB (neurotropin receptor tyrosine kinase B) suppresses voltage gated potassium channel (K v 1.5) via phosphorylation of multiple tyrosine residues (BS Colley et. al 2007 Neuroscience 144:531–46). It is not known how ion channel proteins, which lack catalytic activity, interact with BDNF signaling pathway. In this study we cloned K v 1.5 gene into GFP expressing vector and transfected the gene into HeLa cell with jetPRIME reagent (80 % transfection efficiency). Western blot analysis revealed that the protein expression of K v 1.5 was significantly increased in K v 1.5 over expressing cells as compared to cells which were not transfected. However, with BDNF or 7,8 dihydroxyflavone, a TrkB agonist, the expression of K v 1.5 protein was significantly reduced. We further demonstrated that in K v 1.5 over expressing cells treated with either BDNF or 7,8 dihydroxyflavone, the Akt and STAT‐3 signaling pathways were stimulated. Collectively our findings suggest that increased BDNF activity in K v 1.5 over expressing cells contributes to the reduction in K v 1.5 protein expression and probably the channel functions through TrkB receptor stimulation which triggers Akt and STAT‐3 cell survival pathways. This work is funded by a VA grant.