Nielsen Group - Gap Junction
The research focus of the Gap Junction Group is the regulation of cardiac conduction. We are particularly interested in the role of gap junctions and their use as anti-arrhytmic target.
The work of the Gap Junction Group has contributed to the demonstration that the drug candidate rotigaptide enhanced gap junctional coupling, prevented conduction slowing, reduced rather than increased infarct size and that rotigaptide acted by preventing Cx43 de-phosphorylation.
In later years, the Gap Junction Group has worked on how obesity and pre-diabetes affects cardiac conduction. Metabolic syndrome and diabetic states are associated with arrhythmias and sudden death but underlying causes are still debated.
The group's focus has been on the involvement of conduction disturbances and we have demonstrated that diabetic and pre-diabetic rats have slowed conduction.
Complex multi-cellular organs require coordination of the activity of individual cells. This is accomplished by gap junctions which are clusters of intercellular channels offering low-resistance electrical coupling between cells. The gap junction channels act as water filled pores, allowing current and substances up to ~1 kDa to pass. The proteins forming these channels belong to a family called connexins.
Gap junctions play a role in the propagation of action potentials, and most myocardial cells are extensively coupled. Coupling is essential to both proper activation of the heart and to its electrical stability. This is accomplished by synchronising activation and repolarisation of neighbouring myocytes. A decrease in intercellular coupling has been shown not only to slow conduction, but also to create electrical gradients during repolarisation. These effects will make hearts prone to arrhythmia.