title: Homocysteine augments BK channel activity and decreases exocytosis of secretory granules in rat GH3 cells.
abstract: 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 GH3 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 (HHcy), a disease arising due to abnormally elevated levels of Hcy in the plasma.
authors: Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia.
authors: Aisylu S
authors: AS
authors: Gaifullina
authors: Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia.
authors: Aleksey V
authors: AV
authors: Yakovlev
authors: Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia.
authors: Alsu N
authors: AN
authors: Mustafina
authors: Department of Cell Biology and Physiology, University of Salzburg, Austria.
authors: Thomas M
authors: TM
authors: Weiger
authors: Department of Cell Biology and Physiology, University of Salzburg, Austria.
authors: Anton
authors: A
authors: Hermann
authors: Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia. sitdikovaguzel@gmail.com.
authors: Guzel F
authors: GF
authors: Sitdikova
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D005089:Exocytosis / Q000187:drug effects*; D006710:Homocysteine / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D022142:Secretory Vesicles / Q000187:drug effects* / Q000378:metabolism
chemical_list: D007211:Indoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D006710:Homocysteine; C048220:paxilline; D000111:Acetylcysteine
keywords: BK channels; exocytosis; homocysteine; oxidative stress