title: Unique action of sodium tanshinone II-A sulfonate (DS-201) on the Ca(2+) dependent BK(Ca) activation in mouse cerebral arterial smooth muscle cells.
abstract: Sodium tanshinone II-A sulfonate (DS-201) is a water-soluble derivative of tanshinone IIA, a main active constituent of Salvia miltiorrhiza which has been used for treatments of cardio- and cerebro-vascular diseases. DS-201 activates large conductance Ca(2+)-sensitive K(+) channels (BK(Ca)) in arterial smooth muscle cells, and reduces the vascular tone. Here we investigated the effect of DS-201 on the BK(Ca) channel kinetics by analyzing single channel currents. Smooth muscle cells were freshly isolated from mouse cerebral arteries. Single channel currents of BK(Ca) were recorded by patch clamp. DS-201 increased the total open probability (NPo) of BK(Ca) in a concentration-dependent manner. But this action required intracellular Ca(2+), and the effect depended on the Ca(2+) concentration ([Ca(2+)](free)). DS-201 activated BK(Ca) with the half maximal effective concentration (EC(50)) of 111.5μM at 0.01μM [Ca(2+)](free), and 68.5μM at 0.1μM [Ca(2+)](free.) The effect of DS-201 on NPo was particularly strong in the range of [Ca(2+)](free) between 0.1 and 1μM. Analysis of the channel kinetics revealed that DS-201 had only the effect on the channel closing without affecting the channel opening, which was a striking contrast to the effect of [Ca(2+)](free), that is characterized by changing the channel opening without changing the channel closing. DS-201 may be bound to the open state of BK(Ca), and have an inhibitory effect on the transition from the open to closed state. By this way DS-201 may enhance the activity of BK(Ca), and exhibit a strong vasodilating effect against vasoconstriction in the range of [Ca(2+)](free) between 0.1 and 1μM.
authors.affiliation: Department of Electrophysiology, Institute of Cardiovasology, Luzhou Medical College, Luzhou, Sichuan, 646000, China.
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Tan
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.forename: Pengyun
authors.initials: P
authors.lastname: Li
authors.forename: Isao
authors.initials: I
authors.lastname: Inoue
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zeng
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002536:Cerebral Arteries / Q000166:cytology*; D004553:Electric Conductivity; D007700:Kinetics; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*
chemical_list: C530995:BKCa protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D010616:Phenanthrenes; C024894:tanshinone II A sodium sulfonate; D002118:Calcium