Effects of NIP-141 on K currents in human atrial myocytes.
A novel benzopyran derivative, NIP-141, effectively terminates experimental atrial fibrillation in canine hearts by prolonging atrial refractoriness. However, the effects of this drug on human atrial myocytes are unknown. This experiment evaluated the effects of NIP-141 on K currents in isolated human atrial myocytes using a whole-cell voltage-clamp method. NIP-141 inhibited the transient outward current (I(to)) and the ultra-rapid delayed rectifier K current (I(Kur)), each in a dose-dependent manner, with half-maximal inhibition concentrations of 16.3 microM and 5.3 microM, respectively (n = 5). NIP-141 inhibited both K currents in a voltage- and use-independent fashion, and it preferentially blocked them in the open state and dissociated rapidly from the channel. Because both K currents contribute significantly to the repolarization of the atrial action potential, these findings suggest that NIP-141 may terminate atrial fibrillation by prolonging action potential duration.
Seki
Akiko
A
The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan.
Hagiwara
Nobuhisa
N
Kasanuki
Hiroshi
H
D000200:Action Potentials / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D020517:Atrial Appendage / Q000166:cytology; D001578:Benzopyrans / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D051668:Delayed Rectifier Potassium Channels; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D024642:Potassium Channels, Voltage-Gated; D013997:Time Factors
D001578:Benzopyrans; D051668:Delayed Rectifier Potassium Channels; C449401:NIP 141; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated