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Comment
. 2005 May;145(1):3-4.
doi: 10.1038/sj.bjp.0706143.

Protein trafficking abnormalities: a new mechanism in drug-induced long QT syndrome

Lee L Eckhardt  1 , Sridharan Rajamani, Craig T January
Affiliations
Comment

Protein trafficking abnormalities: a new mechanism in drug-induced long QT syndrome

Lee L Eckhardt et al. Br J Pharmacol. 2005 May.

Abstract

Drug induced long QT syndrome (LQTS) can lead to cardiac arrhythmias and sudden death, and has emerged as a worldwide problem. Most drugs that cause this are thought to directly block a specific cardiac ion channel (KCNH2 or hERG) that carries the rapidly activating delayed rectifier potassium current, I(Kr). In this issue of the British Journal of Pharmacology, evidence is presented to support a new mechanism for causing drug induced LQTS. The drug pentamidine, at near therapeutic concentrations that do not cause direct KCNH2 channel block, disrupts normal KCNH2 channel protein processing and maturation to reduce its surface membrane expression. This indirect mechanism for reducing I(Kr) is novel, and whether other drugs may cause similar protein trafficking abnormalities is largely unknown.

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References

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