Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 598, Issue 1-3, Pages 9-15Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2008.09.013
Keywords
High conductance Ca2+ activated; K+ channel (BKCa); Sodium tanshinoneII-A sulfonate; Porcine coronary artery smooth muscle; Vasodilatation
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Funding
- National Natural Science Foundation of China [39370270, 30370527]
- Sichuan Education Committee Foundation of China [2003A058]
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High conductance Ca2+ activated K+ channels (BKCa) in vascular smooth muscles play important roles in controlling the vascular tone by determining the level of membrane potential and Ca2+ influx through voltage gated Ca2+ channels. Agents that alter the activity of Ca2+ channels or BKCa thus affect the vascular tone in both physiological and pathological conditions. Danshen, the dried root of Salvia miltiorrhiza, is a commonly used traditional Chinese medicine and is widely used as an effective remedy for cardiovascular and cerebral vascular diseases partly by its vasodilatation. Sodium tanshinoneII-A sulfonate (DS-201) is a water-soluble derivative of Tanshinone IIA, the main active component of Danshen. The purpose of this study was to explore possible mechanisms of vasodilative effects of DS-201 using porcine coronary artery smooth muscle. DS-201 induced relaxation of the coronary smooth muscle which had been contracted with 30 mM KCl, and the relaxation was inhibited by 100 nM iberiotoxin (IbTX), a specific BKCa channel blocker. Using perforated whole-cell recordings and single channel recordings, effects of DS-201 on BKCa, were examined. The results showed that DS-201 activated BKCa. Extracellular application of DS-201 at 40, 80 mu M under the whole-cell configuration induced increases of the BKCa, macroscopic currents by 43.6%, 42.1% respectively, and the spontaneous transient outward K+ currents (STOCs) by 48.7%, 47.4% respectively. In inside-out patches, bath application of 20-150 mu M of DS-201 activated BKCa, by 5.4-173.2 fold. These results indicate that the vasodilatation by DS-201 is related to activation of BKCa. (C) 2008 Elsevier B.V. All rights reserved.
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