Defective Tracfficking Of HERG K+ Channels: Risk Stratification In Patients With Long QT Syndrome Type 2.
Funder
National Health and Medical Research Council
Funding Amount
$483,406.00
Summary
Disturbances of the rhythm of the heartbeat are a major cause of death and disability. Due to the sudden onset and rapidity of death with cardiac arrhythmias it is important to be able to predict in advance who is most at risk. In this study we will investigate whether it is possible to develop in vitro assays to stratify risk in patients with congenital long QT syndrome type 2, an inherited arrhythmia syndrome.
State-dependence Of Drug Binding To HERG K+ Channels.
Funder
National Health and Medical Research Council
Funding Amount
$397,224.00
Summary
In recent years, it has become apparent that a wide range of prescription drugs can cause inadvertent inhibition of a potassium channel in the heart known as hERG, resulting in an increased risk of cardiac arrhythmias and death. This has prompted the withdrawal from the market of 9 drugs and the introduction of mandatory testing of all drugs for inhibition of hERG channels. In this proposal we seek a molecular explanation for the promiscuity of drug binding to hERG channels
The hERG potassium ion channel is critical for the maintenance of the normal rhythm of the heartbeat. The aim of this study is to map the temporal sequence of the movements of different parts of the hERG K+ channel that regulate the opening and closing of the extracellular gate of the channel. To achieve this, we will use the powerful protein engineering technique of phi-value analysis, a technique that has never before been applied to voltage-gated ion channels.