Régulation des canaux ioniques par les lipides membranaires

 

Nazzareno D'Avanzo

Université de Montréal

 

Domaine : santé circulatoire et respiratoire

Programme chercheurs-boursiers Junior 1

Concours 2014-2015

Changes in the membrane voltage arising from the co-ordinated movements of ions across the cell through ion channels imbedded in the cell membrane underlie fundamental physiological processes, such as the co-ordinated heartbeat. Mutations of ion channels can cause disorders such as congenital heart failure, and cardiac arrhythmias. Our understanding of ion channel function and pharmacology has led to interventions that dramatically improve quality of life and lifespan for the affected individuals. However, treatment options are less than ideal due to non-specific interactions with other proteins, or because the drug acts to completely inhibit the target protein, when smaller effects would be more desirable. Lipidomics has begun to identify changes in the membrane lipids during the development of cardiac arrhythmias.

Additionally, new appreciation is developing for the regulation of ion channels by the membranes in which they are embedded. Thus, as membrane lipids change during the development of disease, it is likely that the currents through the ion channels will also be altered. This provides a potentially new paradigm to treat arrhythmias, and presents an opportunity to finely-tune the desired changes in ion channel function through therapeutic modulation of the cell membrane. By characterizing how various ion channel families are regulated by membrane using purified protein in model lipid systems lipids, my laboratory aims to identify critical determinants of their function. In turn, we aim to determine the changes in cellular function due to altered lipid-channel interactions in cardiomyocytes during the progression of cardiac arrhythmias and develop methods for therapeutic lipid modulation.