Homocysteine augments BK channel activity and decreases exocytosis of secretory granules in rat GH3 cells
| Autor: | Guzel F. Sitdikova, Aisylu S. Gaifullina, Thomas Weiger, Aleksey V. Yakovlev, Alsu Mustafina, Anton Hermann |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
BK channel Indoles Biophysics Action Potentials medicine.disease_cause Biochemistry Exocytosis Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Structural Biology Potassium Channel Blockers Genetics Extracellular medicine Animals Large-Conductance Calcium-Activated Potassium Channels Paxilline Homocysteine Molecular Biology chemistry.chemical_classification Reactive oxygen species biology Chemistry Secretory Vesicles Potassium channel blocker Cell Biology Secretory Vesicle Acetylcysteine Rats Cell biology 030104 developmental biology biology.protein 030217 neurology & neurosurgery Oxidative stress medicine.drug |
| Zdroj: | FEBS Letters. 590:3375-3384 |
| ISSN: | 0014-5793 |
| DOI: | 10.1002/1873-3468.12381 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text