Activation of high conductance Ca(2+)-activated K(+) channels by sodium tanshinoneII-A sulfonate (DS-201) in porcine coronary artery smooth muscle cells.

High conductance Ca(2+) activated K(+) channels (BK(Ca)) in vascular smooth muscles play important roles in controlling the vascular tone by determining the level of membrane potential and Ca(2+) influx through voltage gated Ca(2+) channels. Agents that alter the activity of Ca(2+) channels or BK(Ca) 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 BK(Ca) channel blocker. Using perforated whole-cell recordings and single channel recordings, effects of DS-201 on BK(Ca) were examined. The results showed that DS-201 activated BK(Ca). Extracellular application of DS-201 at 40, 80 microM under the whole-cell configuration induced increases of the BK(Ca) 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 muM of DS-201 activated BK(Ca) by 5.4-173.2 fold. These results indicate that the vasodilatation by DS-201 is related to activation of BK(Ca).