HERG K^+ Channel Blockade by the Novel Antiviral Drug Sophocarpine(Highlighted paper selected by Editor-in-chief,Pharmacology)

概要

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Human ether-a-go-go-related gene (HERG) encodes the rapid component of the cardiac delayed rectifier K^+ current, which has an important role in the repolarization of the cardiac action potential. QT interval prolongation through HERG channel inhibition is associated with a risk oftorsade de pointes arrhythmias and is a major challenge for drug development. The effects of the novel antiviral drug sophocarpine (SC) were examined on stably expressed HERG channels in human embryonic kidney (HEK293) cells using a whole-cell patch clamp technique, Western blot analysis and immunofluorescence experiments. SC inhibited HERG channels in a concentration-dependent manner, with an IC_<50> of 100-300 μM. SC significantly accelerated channel inactivation, recovery from inactivation and onset of inactivation. In addition, it had no effect on channel activation and deactivation. Based on Western blot and immunofluorescence results, SC had no significant effect on the expression of HERG protein. In summary, SC is a potent blocker of HERG K^+ channels that functions by changing the channel inactivation kinetics. In addition, SC has no effect on the generation and trafficking of HERG protein.
公益社団法人日本薬学会の論文
2008-04-01