Chromanol 293B inhibits slowly activating delayed rectifier and transient outward currents in canine left ventricular myocytes.
BACKGROUND
Drugs that selectively inhibit the slowly activating component of the delayed rectifier potassium current (I(Ks)) are being considered as possible antiarrhythmic agents, because they produce more prolongation of action potential duration at fast rates with less transmural dispersion of repolarization compared with blockers of the rapidly activating component (I(Kr)). Although the chromanol derivative chromanol 293B has been shown to be relatively selective in blocking I(Ks) in some species, its selectivity is far from established.


RESULTS
The present study uses whole-cell, patch-clamp technique to examine the selectivity of this compound for inhibition of I(Ks) in comparison with other repolarizing ionic currents, such as I(Kr), inward rectifier potassium current (I(Kl)), transient outward current (I(to)), and L-type calcium current (I(Ca-L)) in canine left ventricular mid-myocardial and endocardial cells. Chromanol 293B blocked I(Ks) with an IC50 of 1.8 microM and I(to) with an IC50 of 38 microM. Concentrations as high as 30 microM did not affect I(Kl), I(Kr), or I(Ca-L). Higher concentrations of chromanol 293B (100 microM) caused a slight, but statistically insignificant, inhibition of I(Kr).


CONCLUSIONS
Our results indicate that chromanol 293B is a relatively selective blocker of I(Ks) in canine left ventricular myocytes.
Sun
Z Q
ZQ
Masonic Medical Research Laboratory, Utica, New York 13501, USA.
Thomas
G P
GP
Antzelevitch
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D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D027682:Cation Transport Proteins; D002839:Chromans / Q000494:pharmacology*; D051668:Delayed Rectifier Potassium Channels; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D051638:Ether-A-Go-Go Potassium Channels; D005260:Female; D006706:Homeostasis; D020128:Inhibitory Concentration 50; D008297:Male; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*
D020746:Calcium Channels, L-Type; D027682:Cation Transport Proteins; D002839:Chromans; D051668:Delayed Rectifier Potassium Channels; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides; C103474:6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane