The Role Of Calcium And TRPC Channels In Sinoatrial Node Ageing
Funder
National Health and Medical Research Council
Funding Amount
$385,301.00
Summary
The failure of pacemaker function is a common clinical problem in the elderly who become more susceptible to cardiac arrhythmias. We recently discovered a new calcium channel called the transient receptor potential canonical channel (TRPC) in the pacemaker cells. The aim of this research is to study the role of TRPC channels in pacemaker ageing. Improved understanding of the mechanisms of the pacemaker ageing may provide new therapeutic strategies for reducing the risk of cardiac arrhythmias.
Clinical trials and experimental investigations have demonstrated that a diet rich in fish oil, containing high levels of omega 3 fatty acids, provides protection against arrhythmias and sudden cardiac death associated with heart failure. Surprisingly little is known about how these dietary omega 3 lipids alter the electrical and mechanical function of cardiac muscle cells when incorporated into the membrane of these cells. The goal of this study is to examine how experimental omega 3 diet treat ....Clinical trials and experimental investigations have demonstrated that a diet rich in fish oil, containing high levels of omega 3 fatty acids, provides protection against arrhythmias and sudden cardiac death associated with heart failure. Surprisingly little is known about how these dietary omega 3 lipids alter the electrical and mechanical function of cardiac muscle cells when incorporated into the membrane of these cells. The goal of this study is to examine how experimental omega 3 diet treatment can modify the heart muscle cell structure and function. In particular we will determine which cellular mechanisms may be important in conferring selective benefit of dietary intervention on pre-failing heart function. For this study we will use mice which exhibit signs of heart failure induced by hormone overproduction (angiotensin II) and by elevation of blood pressure (by surgical constriction). Mice will be fed omega-3 and omega-6 diets and experiments to investigate cardiac muscle cell structure and function will be carried out using a variety of electrical recording, microscopic and molecular biology techniques. Diet-induced changes in the capacity of the heart cells to regulate calcium will be investigated using cells loaded with fluroescent indicators. Single cell electrical recording techniques (patch clamp) will also be used in combination with ECG measurement to evaluate how arrhythmic activity arising from electrically and mechanically unstable cells can be suppressed by omega-3 diet intervention. Finally we will take the first step towards validating the rodent experimental findings in a clinical setting with measurements of calcium transporters and channel expression in human specimens from cardiac surgery patients.Read moreRead less
How Does Sudden Cardiac Death Occur In Familial Hypertrophic Cardiomyopathy?
Funder
National Health and Medical Research Council
Funding Amount
$1,312,606.00
Summary
Familial hypertrophic cardiomyopathy is a leading cause of sudden cardiac death but the mechanisms for the induction of arrhythmia are unknown. This proposal has the potential to impact sudden death in the young and enable significant expansion of Australia’s research capacity into the treatment of familial hypertrophic heart disease in humans.
The primary aim of my research has been to understand how biological ion channels work. All electrical activities in the nervous system, including communication between cells and influences of hormones and drugs on cell function, are regulated by the opening and closing of ion channels. Thus, understanding how these ion channels operate will ultimately help us find the causes of, and possibly cures for, many neurological, muscular and cardiac disorders.
The L-type Calcium Channel In Cardiovascular Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Calcium influx into cardiac muscle cells occurs via the L-type calcium channel. The channel is essential to life but when function is altered it can contribute to the development of sudden death and heart failure. I have made significant discoveries in understanding the role of the channel in disease and I have exploited this knowledge to design therapy including a novel class of calcium channel antagonists to prevent the development of heart failure.