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Protein trafficking abnormalities: a new mechanism in drug‐induced long QT syndrome
Author(s) -
Eckhardt Lee L,
Rajamani Sridharan,
January Craig T
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706143
Subject(s) - herg , long qt syndrome , potassium channel , drug , mechanism (biology) , pharmacology , ion channel , potassium channel blocker , medicine , torsades de pointes , bioinformatics , biology , qt interval , receptor , philosophy , epistemology
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. British Journal of Pharmacology (2005) 145 , 3–4. doi: 10.1038/sj.bjp.0706143