中国药理学报：英文版, 2014 (11), p.1351-1363
2014
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- Autor(en) / Beteiligte
- Titel
- Tanshinone II.A sodium sulfonate （DS-201） enhances human BKca channel activity by selectively targeting the pore-forming α subunit
- Ist Teil von
- 中国药理学报：英文版, 2014 (11), p.1351-1363
- Erscheinungsjahr
- 2014
- Quelle
- Alma/SFX Local Collection
- Beschreibungen/Notizen
- Aim： Tanshinone II-A sodium sulfonate （DS-201）, a water-soluble derivative of Tanshinone II-A, has been found to induce vascular relaxation and activate BKca channels. The aim of this study was to explore the mechanisms underlying the action of DS-201 on BKca channels. Methods： Human BKca channels containing α subunit alone or α plus β1 subunits were expressed in HEK293 cells. BKca currents were recorded from the cells using patch-clamp technique. The expression and trafficking of BKca subunits in HEK293 cells or vascular smooth muscle cells （VSMCs） were detected by Western blotting, flow cytometry and confocal microscopy. Results： DS-201 （40-160 μmol/L） concentration-dependently increased the total open probability of BKca channels in HEK293 cells, associated with enhancements of Ca2＋ and voltage dependence as well as a delay in deactivation. Coexpression of β1 subunit did not affect the action of DS-201： the values of EC50 for BKca channels containing α subunit alone and α plus β1 subunit were 66.6±1.5 and 62.0±1.1 pmol/L, respectively. In both HEK293 cells and VSMCs, DS-201 （80 pmol/L） markedly increased the expression of αsubunit without affecting α1 subunit. In HEK293 cells, DS-201 enriched the membranous level of α subunit, likely by accelerating the trafficking and suppressing the internalization of α subunit. In both HEK293 cells and VSMCs, DS-201 （≥320 pmol/L） induced significant cytotoxicity. Conclusion： DS-201 selectively targets the pore-forming α subunit of human BKca channels, thus enhancing the channel activities and increasing the subunit expression and trafficking, whereas the β1 subunit does not contribute to the action of DS-201.