ABSTRACT
Several antimalarial drugs are known to produce a QT interval prolongation via a blockade of the rapidly activating delayed rectifier K+ current (IKr), encoded by the human-ether-a-go-go-related gene (hERG). We investigated the influence of lumefantrine and its major metabolite desbutyl-lumefantrine, as well as halofantrine, chloroquine, and mefloquine, on wild type hERG K+ channels in stably transfected human embryonic kidney cells (HEK293) using the whole cell patch-clamp technique. All of the tested antimalarial drugs inhibited the hERG K+ channels in a concentration- and time-dependent manner. Only halofantrine blocked hERG tail currents voltage-dependently. The ranking of the half-maximal inhibitory concentrations (IC50) of the antimalarials was: halofantrine (0.04 microM)Subject(s)
Action Potentials/drug effects
, Antimalarials/pharmacology
, Potassium Channels, Voltage-Gated
, Potassium Channels/physiology
, Transfection
, Action Potentials/genetics
, Antimalarials/chemistry
, Cell Line
, ERG1 Potassium Channel
, Ether-A-Go-Go Potassium Channels
, Humans
, Potassium Channel Blockers/chemistry
, Potassium Channel Blockers/pharmacology
, Potassium Channels/genetics
, Transfection/methods