Okabe K, Kajioka S, Nakao K, Kitamura K, Kuriyama H, Weston A H
Department of Pharmecology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Pharmacol Exp Ther. 1990 Feb;252(2):832-9.
The effects of cromakalim (BRL34915), a novel K channel opener, on ionic currents in dispersed smooth muscle cells of the rat portal vein were investigated. Application of cromakalim (greater than 3 microM) generated an outward current, the reversal potential of which (-79 mV) was almost the same as the theoretical K equilibrium potential (-80 mV) under the experimental conditions used. When the Ca in the physiological salt solution (PSS) was replaced with Mn, the cromakalim-induced outward current was inhibited markedly. When 4 mM ethylene glycol bis(beta-aminoethyl ether(N,N'-N,N'-tetraacetic acid (EGTA) was added to the pipette solution (bath solution, Ca-free PSS + Mn), cromakalim inhibited the outward current evoked by command pulses. Using a pipette solution containing high Cs with 4 mM EGTA and a bath PSS containing 2.5 mM Ca with 1 microM tetrodotoxin, the Ca inward current was isolated. Cromakalim (greater than 3 microM) inhibited the Ca inward current in a voltage- dependent manner. Cromakalim (30 microM) inhibited the Ca inward current to 0.6 times the control. The decay of the inward Ca current comprised fast and slow components. Cromakalim inhibited the latter component and shifted the voltage-dependent inactivation curve of this current to the left (more hyperpolarized direction) in a parallel manner and delayed recovery from inactivation as estimated using a double pulse protocol. By using a pipette solution containing high Cs with 4 mM EGTA and Ca-free PSS containing 2.5 mM Mn in the bath, Na inward currents, blocked by tetrodotoxin (IC50 = 10 nM), were evoked by depolarizing pulses. Cromakalim (up to 30 microM) had no effect on the Na inward current.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了新型钾通道开放剂克罗卡林（BRL34915）对大鼠门静脉分散平滑肌细胞离子电流的影响。应用克罗卡林（大于3μM）产生外向电流，其反转电位（-79mV）与所用实验条件下的理论钾平衡电位（-80mV）几乎相同。当生理盐溶液（PSS）中的钙被锰取代时，克罗卡林诱导的外向电流明显受到抑制。当向吸管溶液（浴液，无钙PSS + 锰）中加入4mM乙二醇双（β-氨基乙醚）-N，N，N'，N'-四乙酸（EGTA）时，克罗卡林抑制指令脉冲诱发的外向电流。使用含有高铯和4mM EGTA的吸管溶液以及含有2.5mM钙和1μM河豚毒素的浴PSS，分离出钙内向电流。克罗卡林（大于3μM）以电压依赖性方式抑制钙内向电流。克罗卡林（30μM）将钙内向电流抑制至对照的0.6倍。内向钙电流的衰减包括快速和慢速成分。克罗卡林抑制后者成分，并以平行方式将该电流的电压依赖性失活曲线向左（更超极化方向）移动，并延迟从失活状态恢复，这是使用双脉冲协议估计的。通过使用含有高铯和4mM EGTA的吸管溶液以及浴中含有2.5mM锰的无钙PSS，通过去极化脉冲诱发被河豚毒素阻断（IC50 = 10nM）的钠内向电流。克罗卡林（高达30μM）对钠内向电流没有影响。（摘要截断于250字）
