Gene Transfer of Nitric Oxide Synthase into Cardiac Nerves Modulates Neurotransmission

Cardiac neurobiology of arrhythmia
Cardiac neurobiology of arrhythmia

The rhythm of the heart is regulated by chemicals released from cardiac nerves (autonomic nerves) that speed up and slow down the rate of beating and contraction. Arrhythmia is often associated with neural imbalance and normally precedes sudden cardiac death. However, we still do not fully understand how the two branches of the cardiac autonomic nervous system communicate and whether their uncoupling is central to the onset of ventricular arrhythmia.

The endogenous gas nitric oxide is now thought to be a key intermediary in cardiac inter/intracellular signalling, where it has been shown to regulate several ion channels that control cardiac function during neural activation. Our aim is to understand the role played by nitric oxide in the control of cardiac sympatho-vagal neurotransmission and myocardial excitability in normal, diseased and exercise trained hearts. Specifically, we are examining whether (i) free radicals and their chemical partners regulate cardiac neurons, and (ii) if uncoupling of proteins that anchor free radicals is central to neural control; (iii) whether targeted gene delivery with free radical enzymes.

To do this we employ an integrated approach: by studying the molecular and electrical properties of cardiac tissue in-vitro and in-vivo using gene transfer, western/northern blotting techniques, electrophysiological recordings (single cell to multi-electrode array mapping) and network models to reconstruct (using parallel computing) biophysical events. We encourage students to use a broad range of techniques to facilitate the integration of their results back into whole systems.

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