Dr Cherrie H.T. Kong

I am interested in understanding cardiac excitation-contraction coupling (ECC), which is a set of cellular processes that allow muscle cells to generate force in response to electrical stimulation. ECC must occur without fail at every heartbeat; if compromised, the heart can fail and death result. A quantitative understanding of the underlying mechanisms allows us to examine how changes affect disease progression and how they might be slowed or reversed to prevent heart failure.

Calcium (Ca) signalling is crucial to cardiac ECC. When the electrical signal arrives at a ventricular muscle cell, it is detected by Ca channels in the cell membrane. These channels allow Ca to enter the cell which contribute to the electrical behaviour of the cell as well as activate a several of key processes. Ca not only regulates gene expression but also causes the release of extra Ca from an internal Ca store called the sarcoplasmic reticulum. It is this Ca release from the internal store that regulates the force of contraction. 

The mechanisms that determine the release of Ca from the store has been a central component of my work over several years. We know that the surface membrane Ca channels are concentrated in transverse tubules (TTs), a complex network of cell membrane invaginations that help to distribute cell surface activities throughout the cell interior. The internal store has different Ca channels called ryanodine receptors (RyRs) that are concentrated in clusters that are close to TTs and their activation is observed as a spatiotemporally localised burst of Ca called a “Ca spark”. Importantly, these RyR clusters can become disrupted in heart failure so that cross signalling between themselves and other Ca dependent processes becomes compromised. 

To study how these processes work efficiently in health and become compromised in heart failure, I use electrophysiology, high resolution imaging/analysis and computer modelling techniques. The ability to obtain quality experimental data as well as develop novel measurement tools/computer models is a powerful way to clarify the interplay of the unique structural and functional properties of cardiac ECC. For example, how is the positive feedback mechanism, that makes sure the internal store releases adequate Ca, affected by structural changes and how may we offset such changes to treat disease?