Characterisation And Regulation Of Chloride Channels In Cardiac And Skeletal Sarcoplasmic Reticulum In Mammals
Funder
National Health and Medical Research Council
Funding Amount
$381,856.00
Summary
An understanding of the operation of ion channels in cell membranes is fundamental to our knowledge of the function of muscles under normal conditions and in pathological states that modify cell function, e.g. myotonia and cardiac failure. Ion channels control the flow of currents and the transport of substances which ultimately determine whether cells live or die, and hence whether cell pathologies are expressed as muscle failure, as when hypoxia causes tissue damage to the heart, or as severe ....An understanding of the operation of ion channels in cell membranes is fundamental to our knowledge of the function of muscles under normal conditions and in pathological states that modify cell function, e.g. myotonia and cardiac failure. Ion channels control the flow of currents and the transport of substances which ultimately determine whether cells live or die, and hence whether cell pathologies are expressed as muscle failure, as when hypoxia causes tissue damage to the heart, or as severe arrythmia or cardiac arrest. The objective is to understand channel involvement in the mechanisms underlying the function of cardiac and skeletal muscle. We believe that by mimicking the factors that occur in pathological conditions we can understand how ion channels are altered and controlled, and find ways of reversing harmful alterations, thereby reversing cell damage and failure of vital muscle function.Drugs will be used to modify the 'gating' of the channels. By comparing the effects of different drugs, we hope to determine the important features of the mechanisms that control the gating of the channels, making them more or less sensitive to different influences, especially those that occur in pathological states. The study has great application to the study of other pathologies, e.g. cystic fibrosis, severe diarrhoea, paralysis and chronic fatigue. The pharmacological emphasis offers the fundamental science needed to design novel and specific drugs to combat the many serious pathologies related to ion channel effects. Aside from its importance to basic science and to immediate issues of health, the study offers considerable economic gains, both through improved public health and through development of pharmaceuticals.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