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.
Molecular Basis Of Voltage Dependent-activation Of HERG K+ Channels
Funder
National Health and Medical Research Council
Funding Amount
$439,500.00
Summary
The rhythm of the normal heart beat is controlled by electrical signals mediated by the flow of electrically charged atoms called ions. The flow of ions across heart cell membranes is predominantly mediated by proteins called ion channels that open and close in response to changes in the voltage across the cell membrane. One of these channels, called the HERG channel, has some unusual properties. Most notably, HERG channels open very slowly following an electrical stimulus, so slowly that they d ....The rhythm of the normal heart beat is controlled by electrical signals mediated by the flow of electrically charged atoms called ions. The flow of ions across heart cell membranes is predominantly mediated by proteins called ion channels that open and close in response to changes in the voltage across the cell membrane. One of these channels, called the HERG channel, has some unusual properties. Most notably, HERG channels open very slowly following an electrical stimulus, so slowly that they do not fully open until the end of the cardiac contraction cycle. These channels are therefore particularly well placed to help suppress arrhythmias initiated by premature or ectopic beats. We propose to undertake a detailed investigation into the mechanisms by which HERG channels open and close and to determine why activation of these channels is so slow. These results will provide a greater understanding of how HERG channels work and how the normal activity of HERG channels helps to suppress abnormal heart rhythms.Read moreRead less
The rhythm of the normal heart beat is controlled by electrical signals mediated by the flow of ions. The movement of ions across heart cell membranes is predominantly mediated by ion channel proteins. One of these proteins, called HERG, has some very unusual properties that make it well suited for suppressing abnormal heart beats. We propose to undertake a detailed investigation of the mechanisms by which HERG channels open and close. The results will provided a greater understanding of how HER ....The rhythm of the normal heart beat is controlled by electrical signals mediated by the flow of ions. The movement of ions across heart cell membranes is predominantly mediated by ion channel proteins. One of these proteins, called HERG, has some very unusual properties that make it well suited for suppressing abnormal heart beats. We propose to undertake a detailed investigation of the mechanisms by which HERG channels open and close. The results will provided a greater understanding of how HERG channels work and how altered function of HERG channels in patients with heart disease leads to an increased risk of abnormal heart rhythms and sudden cardiac death.Read moreRead less
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
State Dependent Drug Binding To The Human Ether-à-go-go Related Gene Channel
Funder
National Health and Medical Research Council
Funding Amount
$33,193.00
Summary
Heart rhythm disturbance is a common cause of death in our community. In a subset of patients the heart rhythm disturbance is caused by mutations in genes that encode for special proteins called ion channels. However, even in patients without a mutation certain drugs can cause the same problem. Such drugs need to be identified early in their development but current methods to do this are inaccurate. An understanding of how these drugs disturb the heart rhythm will allow more accurate testing.
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.
Improving Long-term Mortality Rates Following Sepsis.
Funder
National Health and Medical Research Council
Funding Amount
$99,682.00
Summary
It is estimated that 37.9 million patients survive sepsis each year. Studies have demonstrated that among patients who survive for 30 days after admission for sepsis, over 40% die in the following two years. There are currently no guidelines that provide recommendations on post-hospital management of sepsis. This research programme aims to identify those patients at greatest risk of death and implement post-sepsis care with the aim to significantly reduce long-term mortality after sepsis.
Longitudinal Communication Outcomes Following Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$798,171.00
Summary
Traumatic brain injury (TBI) is the leading cause of disability in young Australians. The condition frequently manifests in impaired verbal communication. Communication is essential to successful rehabilitation, and return to society. However, the critical time for delivery of optimal treatment for communication remains unknown. This prospective longitudinal study will examine communication recovery following (TBI) to identify predictors of recovery and the best time to offer treatment.