Calcium-dependent inhibition of the sodium-calcium exchange current by KB-R7943.
The inhibitory effect of KB-R7943 (previously called No 7943) on the outward sodium-calcium exchange current was re-examined by applying the drug after inducing the outward exchange current rather than before the current onset as has been done previously. The outward exchange current was induced by raising the extracellular calcium ion concentration, [Ca2+]o, from 0.15 mM to 1.8 mM instead of from 0 mM to 1 mM, as has been done previously. Aftertreatment KB-R7943 inhibited the outward exchange current, and the concentration of KB-R7943 required to inhibit 50% of the exchange current [IC50] was approximately 3 microM. This value is 10 times higher than that obtained by pretreatment of the drug at 1 mM [Ca2+]o. The new IC50 of 3 microM is close to the values for the calcium current (8 microM) and the inward rectifier potassium current (7 microM) but is still significantly lower than that for the inward sodium-calcium exchange current (17 microM).
Watano
T
T
Department of Pharmacology, Fukushima Medical College, Japan.
Kimura
J
J
D000818:Animals; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D009206:Myocardium / Q000166:cytology*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors* / Q000187:drug effects; D013890:Thiourea / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D019831:Sodium-Calcium Exchanger; D013890:Thiourea