We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The Natural Flavone Acacetin Blocks Small Conductance Ca<sup>2 </sup>-Activated K<sup> </sup> Channels Stably Expressed in HEK 293 Cells.
- Authors
Kui-Hao Chen; Hui Liu; Hai-Ying Sun; Man-Wen Jin; Xiao-Guo Sheng; Yan Wang; Gui-Rong Li
- Abstract
The natural flavone acacetin inhibits several voltage-gated potassium currents in atrial myocytes, and has anti-atrial fibrillation (AF) effect in experimental AF models. The present study investigates whether acacetin inhibits the Ca2+-activated potassium (KCa) currents, including small conductance (SKCa1, SKCa2, and SKCa3), intermediate conductance (IKCa), and large-conductance (BKCa) channels stably expressed in HEK 293 cells. The effects of acacetin on these KCa channels were determined with a wholecell patch voltage-clamp technique. The results showed that acacetin inhibited the three subtype SKCa channel currents in concentration-dependent manner with IC50 of 12.4 μM for SKCa1, 10.8 μM for SKCa2, and 11.6 μM for SKCa3. Site-directed mutagenesis of SKCa3 channels generated the mutants H490N, S512T, H521N, and A537V. Acacetin inhibited the mutants with IC50 of 118.5 μM for H490N, 275.2 μM for S512T, 15.3 μM for H521N, and 10.6 μM for A537V, suggesting that acacetin interacts with the P-loop helix of SKCa3 channel. However, acacetin at 3-10 μM did not decrease, but induced a slight increase of BKCa (C70 mV) by 8% at 30 μM. These results demonstrate the novel information that acacetin remarkably inhibits SKCa channels, but not IKCa or BKCa channels, which suggests that blockade of SKCa by acacetin likely contributes to its anti-AF property previously observed in experimental AF.
- Subjects
FLAVONES; ATRIAL fibrillation; MUSCLE cells
- Publication
Frontiers in Pharmacology, 2017, p1
- ISSN
1663-9812
- Publication type
Academic Journal
- DOI
10.3389/fphar.2017.00716