EFFECTS OF CARDIAC DRUGS ON SODIUM-CALCIUM EXCHANGER

(1) KB-R7943 is a drug we first reported to inhibit Na-Ca exchange current (iNCX) with IC - D250 - D2μM for outward iNCX and with 17μM for inward iNCX when one directional iNCX flows. However，在实验条件下，bi-directional iNCX flows. The drug inhibits both outward andinward iNCX equipotently. This result可以explained by different conformation between the bindingforms for external Na and Ca.(2) A new cardioprotective drug, JTV-519 inhibited Na-, Ca-，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 - D250 - D2for Na-current was 2 μM at - 90mv and 1.2 μM at - 60mv . The drug shortened The plateau of The actionpotential.(3) Butanedione monoxime (BDM) inhibited iNCX in guinea pig ventricular cells.IC - d - 250 value was 2.4 mM. A similar drug, pralidoxime also inhibited iNCX，indicating that dephosphorylation of the exchange er may be a reason.我们是目前的投资mutated NCX for the mechanism of the drug action.(4) Class III antiarrhythmic drug，amiodarone inhibits iNCX. IC - D250 - D2 was 3 μM. Trypsin in the pipette solution diminished theinhibitory effect of amiodaroneindicating that the drug affects internal side of the exchange .(5) Anti-diabetic drug，troglitazone inhibited -type Ca current in guinea pig ventricular cells. The effect wasvoltage-dependent. IC - D250 - D2 values were 0.8 μM at a holding potential of -50 mV and larger than10 μM at - 80mv。

(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.