Basic Investigations on the Role of Connexin Hemichannels as an Arrhythmogenic Substrate in Ventricular Arrhythmia

Physiology Group

 

Project 1

Basic Investigations on the Role of Connexin Hemichannels as an Arrhythmogenic Substrate in Ventricular Arrhythmia

Aims

  • The overall aim is to increase our understanding of Cx43 hemichannel gating and its consequent effects in the diseased myocardium, to explore the involvement of dysfunctional hemichannel opening in abnormal cardiac excitation and to determine their role as a potential target for therapeutic intervention to treat cardiac arrhythmia.
  • To develop a cardiac electrophysiology model incorporating numerical simulations of voltage- and calcium-dependent hemichannel activation as well as intracellular calcium dynamics shaped by hemichannel-faciliated calcium entry.
  • To determine how hemichannel remodeling in ischemic cardiomyopathy participates in the generation of abnormal trigger activities in single cells and the destabilization of cardiac electrical wave propagation in multicellular preparations.
  • To determine whether targeting Cx43 hemichannels improves electrical stability of the heart, conferring an anti-arrhythmic effect in ischemic cardiomyopathy.

Funding Ageny

Research Foundation - Flanders (FWO) Research Project 2018-2021, PI Luc Leybaert

Contact

Luc Leybaert

Maarten De Smet