Block of HERG current expressed in HEK293 cells by the Na+-channel blocker cibenzoline

• Published in: Heart and vessels Vol. 19; no. 3; pp. 137 - 143
• Main Authors: Hiramatsu, Mikio, Wu, Long-Mei, Hirano, Yuji, Kawano, Seiko, Furukawa, Tetsushi, Hiraoka, Masayasu
• Format: Journal Article
• Language: English
• Published: Japan Springer Nature B.V 01.05.2004
• Subjects: Action Potentials - drug effects; Animals; Anti-Arrhythmia Agents - pharmacology; Cell Line; Cells; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; Genes; Humans; Imidazoles - pharmacology; Patch-Clamp Techniques; Potassium; Potassium Channels - drug effects; Potassium Channels - genetics; Potassium Channels, Voltage-Gated; Sodium Channel Blockers - pharmacology; Transfection
• ISSN: 0910-8327; 1615-2573
• DOI: 10.1007/s00380-003-0750-8

A Na(+)-channel blocker, cibenzoline, blocks the delayed rectifier potassium current ( I(k)), but its detailed action on the rapidly activating component ( I(kr)) of I(k) encoded by the human ether-a-go-go-related gene ( HERG) has not been clarified. We examined the effects of cibenzoline on stably expressed HERG current in HEK293 cells recorded by the patch-clamp technique of whole-cell configuration. Cibenzoline blocked HERG current expressed in HEK293 cells with IC(50) = 3.7 +/- 0.963 micro M and Hill coefficient = 0.74 +/- 0.12. Voltage-depended activation was shifted in a negative direction by cibenzoline. No block or minor block was induced at test depolarization of -40 to -30 mV, and the block increased with depolarization reaching a plateau at 0 mV without a further increase at positive voltages. Voltage-dependent activation of HERG currents became faster at negative test voltages but there were no changes at positive voltages after cibenzoline. No frequency-dependent block of HERG tail current by cibenzoline after equilibration was noted between 1.33 and 0.2 Hz. Steady-state inactivation of the HERG current was shifted in a negative direction by approximately 8 mV but the time constants of fast inactivation were little affected by cibenzoline. Cibenzoline blocks the I(kr)-like current reconstituted by HERG clone transfection with an IC(50) value comparable to therapeutic concentrations. Cibenzoline has a preferential affinity, at least, to the open state of the HERG channel with a rapid access to the binding site.