Anatomy, Physiology and Human Biology

Cardiovascular Electrophysiology

Further Information

Contact a supervisor for detailed information on student research projects

Professor Livia Hool 
Professor Liva Hool

Currently, cardiovascular disease accounts for 32 % of all deaths in Australia. This is a staggering proportion and continues to exceed death from all cancers combined (30%) and from road deaths (4%). A number of the deaths in the cardiovascular group are due to arrhythmia or disturbances in the electrical activity in the heart.
The normal electrical activity in the heart is controlled by the movement of ions through specialised channels in the membranes of cardiac cells. The autonomic nervous system plays an essential role in regulating cardiac function and many of its effects are mediated via sympathetic neurotransmitters that regulate the activity of these ion channels.
Certain pathophysiological conditions contribute to arrhythmias such as hypoxia and oxidative stress. Under these conditions there is a reduction in blood flow to the muscle in the heart resulting in a reduction in available oxygen and reactive oxygen species production. This is then followed by an increase in generation of reactive oxygen species. There is increased sympathetic drive and the heart has a greater vulnerability to sudden cardiac death. Understanding how cardiac ion channels are regulated under these conditions is crucial to understanding the ionic mechanisms involved in the triggering of ischemic arrhythmias. In addition an increase in reactive oxygen species can contribute to the development of cardiac hypertrophy (enlarged heart) and cardiac failure. We have good evidence that an early mechanism involves increased calcium influx through the L-type calcium channel.
The laboratory uses molecular biology techniques for expression and purification of ion channel protein and biochemical techniques for assay of generation of reactive oxygen species and cell viability. The method that will be used to study membrane currents is the patch-clamp technique. This technique is an extremely powerful method for studying the electrophysiological properties of biological membranes and its contribution to the advancement of research was justly recognised with the awarding of the Nobel Prize in Physiology or Medicine in 1991 to its developers Erwin Neher and Bert Sakmann. The technique can be used to study ion channels both at a whole-cell level or at the level of a single channel. In addition, since the intracellular composition of the cell can be controlled, this can be exploited to determine any second messengers involved. Patch-clamp technique is also used in the laboratory in conjunction with fluorescent dyes to record changes in intracellular calcium, reactive oxygen species generation and mitochondrial function.

How does the L-type calcium channel regulate mitochondrial function in pathology where actin filaments are disrupted?

(Collaboration with Professor Chris Semsarian, Sydney University, Professor Christine Seidman, Harvard University)

Project Outline

Mitochondrial respiration is abnormal in hearts where actin or cytoskeletal proteins are disrupted and it is not understood why. This project follows from data generated by previous students in the lab. We have evidence that the L-type calcium channel can regulate mitochondrial function via the actin cytoskeleton. The project involves the use of patch clamp technique to study L-type calcium channel currents in mouse myocytes isolated from hearts of mice with disease involving disruption in cytoskeletal proteins and fluorescent detection of changes in mitochondrial membrane potential, NADH and superoxide production after activation of the channel. Alterations in expression of proteins in mdx mouse hearts that co-immunoprecipitate with the channel (assessed by Mass Spec) will be identified using immunoblot analysis.   

Project is suitable for

Honours, Masters and PhD

Supervisor

Prof Livia Hool

Essential qualifications

For Honours: An appropriate undergraduate degree with a minimum weighted average of 65% in the level 3 subjects that comprise the relevant major, from an approved institution. Applicants will be assessed on a case-by-case basis.

For Masters or PhD : An appropriate Honours degree or equivalent research experience from an approved institution. Applicants will be assessed on a case-by-case basis.

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How does oxidative stress alter the sensitivity of the L-type calcium channel to isoproterenol? What effect does this have on the action potential?

(Collaboration with Professor Yoram Rudy, University of Washington, St Louis, Missouri, USA)

Project Outline

This question seeks to understand how arrhythmias occur during ischemia/reperfusion in the heart (after a heart attack). Isoproterenol is a beta- adrenergic agonist (and mimics the effects of catecholamines such as adrenaline in the heart). This project will use patch clamp technique to study the effect of oxidative stress and isoproterenol on L- type calcium channel currents in addition to K and Na channel currents and record changes in action potentials. Information gained from patch-clamp studies are incorporated into the Rudy-Luo model. Changes in action potential configuration are modeled and the relative risk of arrhythmia is determined

Project is suitable for

Honours, Masters and PhD

Supervisor

Prof Livia Hool

Essential qualifications

For Honours: An appropriate undergraduate degree with a minimum weighted average of 65% in the level 3 subjects that comprise the relevant major, from an approved institution. Applicants will be assessed on a case-by-case basis.

For Masters or PhD : An appropriate Honours degree or equivalent research experience from an approved institution. Applicants will be assessed on a case-by-case basis.

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