Structure and Function of the Atria of the Heart
My research focus is the atria of the heart and how it functions in both health and disease. Far less is known about the atria compared to the well-studied ventricle despite the prevalence of atrial disease. In the ventricle structures called transverse (t)-tubules are important for controlling the rise in intracellular calcium which makes cells contract. T-tubules were thought to be absent from the atria but we identified an extensive atrial t-tubule network and highlighted their functional importance. We are continuing work to help us understand how t-tubules and other cellular proteins control the rise in intracellular calcium in the atria.
Atrial Transverse tubules in Heart Failure and Development
We have shown that atrial t-tubules are almost completely lost at the point of heart failure. The loss of t-tubules plays a role in the decreased rise of intracellular calcium in the atria associated with this disease and alters the spatial properties of calcium release. We are currently investigating how the change in atrial cellular structure affects the electrical characteristics of the atria and if these changes predispose to the development of arrhythmias. Interestingly t-tubules can be restored to heart cells although they are highly disordered. Our ongoing work tests if recovered t-tubules are able to work properly to fully restore function to the atria.
In order to restore t-tubules therapeutically it is necessary to understand the process by which they are ‘built’. Current projects aim to elucidate pathways and proteins responsible for atrial t-tubule loss in heart failure and restoration following recovery from heart failure. In addition we have mapped the process of normal atrial t-tubule development and again current work is focused on understanding the pathways responsible for normal t-tubule growth.
Atrial Fibrillation (AF), Alternans and the Aged Heart
Atrial fibrillation is the most common cardiac arrhythmia and is most prevalent in the elderly. We have demonstrated some fascinating changes occurring in cellular calcium homeostatic mechanisms in the aged atria and ventricle of the heart. While a number of these changes would be expected to render the aged heart more susceptible to arrhythmias and heart failure others may be protective. Understanding these mechanisms is likely to be of critical importance for our understanding of how and why dysfunction may arise in the aged heart as well as the development of therapeutic strategies to modulate function. Current work is focused on understanding how AF could be triggered at the cellular and in-vivo level and understanding the changes in electrical function and calcium handling in both the young and elderly atria. Our recent work suggests alternans (a beat to beat variation in the atrial action potential) may play an important role in atrial dysfunction in the elderly. Ongoing work is focused on understanding how alternans may arise in this setting.
Cardiac cellular electrophysiology - use of the patch clamp technique on single cardiac myocytes to investigate changes in membrane currents or action potentials.
Intracellular ion measurements - the use of fluorescence to measure changes in calcium or sodium inside the cardiac myocyte.
Western Blot - used to investigate protein expression of ion channels in cardiac tissue.
Confocal Microscopy - used to view cellular structure and the associated rise in intracellular calcium
Super resolution microscopy - state of the art microscopy to understand the ultrastructure of cardiac t-tubules and associated proteins