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Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels.
Naunyn Schmiedebergs Arch Pharmacol. 1999 Mar; 359(3):212-9.NS

Abstract

The human ether-a-go-go-related gene (HERG) encodes a K+ channel with biophysical properties nearly identical to the rapid component of the cardiac-delayed rectifier K+ current (I(Kr)). HERG channels are one primary target for the pharmacological management of arrhythmias. In this study, we investigated the acute effects of the class III antiarrhythmic drug amiodarone on HERG channels expressed heterologously in Xenopus oocytes by use of the two-microelectrode voltage clamp technique. Amiodarone blocked HERG channels with an IC50 of 9.8 microM with a maximum outward tail current reduction of 62.8%. The block consisted of two main components, a closed channel block that could not be reversed within the time of experiments and an open channel block with a slow unblock, having a recovery time constant of 73 s at -80 mV. Inactivation of the HERG channel at very positive potentials could not prevent amiodarone block. These results indicate that HERG channels can be blocked by amiodarone in closed, open and inactivated states. The block of open channels was cumulative, use-dependent and voltage-dependent. In summary, our data suggest that the strong class III antiarrhythmic action of amiodarone is at least partially based upon its acute inhibitory effects on HERG potassium channels.

Authors+Show Affiliations

Department of Cardiology, Medical Hospital, University of Heidelberg, Germany. johann kiehn@UKL.uni-heidelberg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10208308

Citation

Kiehn, J, et al. "Inhibitory Effects of the Class III Antiarrhythmic Drug Amiodarone On Cloned HERG Potassium Channels." Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 359, no. 3, 1999, pp. 212-9.
Kiehn J, Thomas D, Karle CA, et al. Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels. Naunyn Schmiedebergs Arch Pharmacol. 1999;359(3):212-9.
Kiehn, J., Thomas, D., Karle, C. A., Schöls, W., & Kübler, W. (1999). Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels. Naunyn-Schmiedeberg's Archives of Pharmacology, 359(3), 212-9.
Kiehn J, et al. Inhibitory Effects of the Class III Antiarrhythmic Drug Amiodarone On Cloned HERG Potassium Channels. Naunyn Schmiedebergs Arch Pharmacol. 1999;359(3):212-9. PubMed PMID: 10208308.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels. AU - Kiehn,J, AU - Thomas,D, AU - Karle,C A, AU - Schöls,W, AU - Kübler,W, PY - 1999/4/20/pubmed PY - 1999/4/20/medline PY - 1999/4/20/entrez SP - 212 EP - 9 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch. Pharmacol. VL - 359 IS - 3 N2 - The human ether-a-go-go-related gene (HERG) encodes a K+ channel with biophysical properties nearly identical to the rapid component of the cardiac-delayed rectifier K+ current (I(Kr)). HERG channels are one primary target for the pharmacological management of arrhythmias. In this study, we investigated the acute effects of the class III antiarrhythmic drug amiodarone on HERG channels expressed heterologously in Xenopus oocytes by use of the two-microelectrode voltage clamp technique. Amiodarone blocked HERG channels with an IC50 of 9.8 microM with a maximum outward tail current reduction of 62.8%. The block consisted of two main components, a closed channel block that could not be reversed within the time of experiments and an open channel block with a slow unblock, having a recovery time constant of 73 s at -80 mV. Inactivation of the HERG channel at very positive potentials could not prevent amiodarone block. These results indicate that HERG channels can be blocked by amiodarone in closed, open and inactivated states. The block of open channels was cumulative, use-dependent and voltage-dependent. In summary, our data suggest that the strong class III antiarrhythmic action of amiodarone is at least partially based upon its acute inhibitory effects on HERG potassium channels. SN - 0028-1298 UR - https://www.unboundmedicine.com/medline/citation/10208308/Inhibitory_effects_of_the_class_III_antiarrhythmic_drug_amiodarone_on_cloned_HERG_potassium_channels_ L2 - https://dx.doi.org/10.1007/pl00005344 DB - PRIME DP - Unbound Medicine ER -