EFFECTS OF CARDIAC DRUGS ON SODIUM-CALCIUM EXCHANGER

（1） KB-R7943是我们第一个报告抑制Na-Ca交换当前（iNCX）的药物，IC-D250-D2为0.3 μM的药物，而当一个方向iNCX流时，KB-R7943是一个抑制iNCX的药物。However，在双方向iNCX流的实验条件下。药物抑制剂两者都是外向和内向的iNCX。这一结果可以通过外部Na和Ca的结合形式之间的不同结构来解释。（2）一种新的心脏活性药物，JTV-519抑制的Na-，Ca-，以及几内亚猪心脏垂直细胞中不受欢迎的K-currents。“Na Current的块，是一个电压-和依赖于使用的块，而且更类似于Quinidine而不是Lidocaine。”IC型D250型D2在-90 mV和1.2 μ M在-60 mV时为2微米。药物已经减少了其行动潜力的平台。（3） Butanedione monoxime （BDM） inhibited iNCX in guinea pig ventricular cells。IC-D250-D2值为2.4毫米，类似药物， pralidoxime也是抑制iNCX，表明交换器的解磷作用可能是一个原因。我们目前正在研究突变的NCX，以促进药物行动的机制。（4） Class III antiarrhythmic drug， amiodarone inhibits iNCX。IC型D250型D2 was 3 μM。Trypsin在管子溶液中减少了抑制剂对阿米odarone的影响，表明药物对交换剂内部的影响。（5）抗糖尿病药物， troglitazone抑制的L型Ca Current in guinea pig ventricular cell。这种影响是依赖于电压的。IC-D250-D2 values were 0.8-M at a holding potential of-50 mV and larger than 10-M at-80 mV。

(1) KB-R7943 is a drug we first reported to inhibit Na-Ca exchange current (iNCX) with ICィイD250ィエD2 0.3 μM for outward iNCX and with 17μM for inward iNCX when one directional iNCX flows. However, under an experimental condition where bi-directional iNCX flows. The drug inhibits both outward and inward iNCX equipotently. This result can be explained by different conformation between the binding forms for external Na and Ca.(2) A new cardioprotective drug, JTV-519 inhibited Na-, Ca-, and inwardly rectifying K-currents in guinea pig cardiac ventricular cells. The block of Na current, was voltage- and use-dependent and was similar to quinidine rather than to lidocaine. ICィイD250ィエD2 for Na-current was 2 μM at -90 mV and 1.2 μM at -60 mV. The drug shortened the plateau of the action potential.(3) Butanedione monoxime (BDM) inhibited iNCX in guinea pig ventricular cells. ICィイD250ィエD2 value was 2.4 mM. A similar drug, pralidoxime also inhibited iNCX, indicating that dephosphorylation of the exchanger may be a reason. We are currently investigating mutated NCX for the mechanism of the drug action.(4) Class III antiarrhythmic drug, amiodarone inhibits iNCX. ICィイD250ィエD2 was 3 μM. Trypsin in the pipette solution diminished the inhibitory effect of amiodarone, indicating that the drug affects internal side of the exchanger.(5) Anti-diabetic drug, troglitazone inhibited L-type Ca current in guinea pig ventricular cells. The effect was voltage-dependent. ICィイD250ィエD2 values were 0.8 μM at a holding potential of -50 mV and larger than 10 μM at -80 mV.