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Homocysteine augments BK channel activity and decreases exocytosis of secretory granules in rat GH 3 cells
Author(s) -
Gaifullina Aisylu S.,
Yakovlev Aleksey V.,
Mustafina Alsu N.,
Weiger Thomas M.,
Hermann Anton,
Sitdikova Guzel F.
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12381
Subject(s) - exocytosis , bk channel , chemistry , endocrinology , medicine , extracellular , hyperhomocysteinemia , microbiology and biotechnology , potassium channel , homocysteine , secretion , biochemistry , biology
In this study, we investigated the effects of L‐homocysteine (Hcy) on maxi calcium‐activated potassium ( BK ) channels and on exocytosis of secretory granules in GH 3 rat pituitary‐derived cells. A major finding of our study indicates that short‐term application of Hcy increased the open probability of oxidized BK channels in inside‐out recordings. Whole‐cell recordings show that extracellular Hcy also augmented BK currents during long‐term application. Furthermore, Hcy decreased the exocytosis of secretory granules. This decrease was partially prevented by the BK channel inhibitor paxilline and fully prevented by N‐acetylcysteine, a reactive oxygen species scavenger. Taken together, our data show that elevation of cellular Hcy level induces oxidative stress, increases BK channel activity, and decreases exocytosis of secretory granules. These findings may provide insight into some of the developmental impairments and neurotoxicity associated with Hyperhomocysteinemia ( HH cy), a disease arising due to abnormally elevated levels of Hcy in the plasma.