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Pathophysiology of cellular excitability

Principal investigator :
Stéphane Hatem, MD, PhD

Research team :

Pascale Guicheney, Michel Komajda, Eric Villard, Julien Amour, Monique Dufhilo, Elise Balse, Philippe Charron, Bruno Riou.

 

[See all of Prof. Hatem’s videos here]

Cellular and molecular electrophysiology explore the electrical properties of cells and tissues, down to the molecular level. They share common concepts and methodological approaches and constitute a rapidly evolving field of research.

Our team brings together biologists and physiologists with a specific expertise in cellular electrophysiology of various native tissues. It is organized around 4 working themes, leveraging a common know-how in developing electrophysiological and imaging approaches from the molecular up to the whole organ level:

1. Identification of mechanisms underlying cardiac ion channel trafficking and their role in the pathophysiology of atrial fibrillation;

2. Molecular determinants of Kir K+ channels and their involvement in the kidney disease sesame syndrome;

3. Mutation of chloride channels and Dente’s kidney disease;

4. Biology of the substrate of atrial fibrillation in which ion transport across membrane is altered.

We nurture strong and fruitful interactions with clinicians and have privileged access to human bio-resources. This is instrumental in translating scientific knowledge into therapeutic innovation that truly benefits patients.

FOCUS

We are mainly interested in 2 health issues: cardiac arrhythmias, with an emphasis on atrial fibrillation (AF), and ion-transport-related kidney diseases.

BIOSKETCH

Prof. Stéphane N. Hatem, MD, PhD, is Director of Research at INSERM and Full Professor of Physiology at the Pitié-Salpêtrière Hospital and at UPMC. After his residency in cardiology, he graduated with a PhD in cardiac cellular electrophysiology from the University of Pennsylvania. He has been heading an INSERM/UPMC Research Lab dedicated to the study of cardiac diseases since 2004.

Prof. Hatem contributed to characterize the structural and functional properties of the atrial myocardium and their alterations during atrial fibrillation (AF). He demonstrated that the substrate of atrial fibrillation precedes the occurrence of arrhythmias and is favoured by atrial dilation, heart failure or ageing. He described mechanisms responsible for the down regulation of the calcium current of atrial myocytes during atrial fibrillation. His team was first to report a coupling between CaMKII and potassium currents in human atrial myocytes. It deciphered the role of the anchoring MAGUK proteins in the heart and described the role played by membrane cholesterol in the regulation of exocytosis of Kv potassium channels.

Prof. Hatem published over 90 peer-reviewed publications. He is the European Coordinator for the 2014 Transatlantic Networks of Excellence Awards on Structural alterations in the myocardium and the substrate for cardiac fibrillation, and a member of the European Network for Translational Research on Atrial Fibrillation (EUTRAF). He has been involved with ICAN since its inception.


Publications

Epicardial adipose tissue and atrial fibrillation
Stéphane N. Hatem, Prashanthan Sanders
Cardiovascular Research (2014) 102, 205–213
doi:10.1093/cvr/cvu045

Shear stress triggers insertion of voltage-gated potassium channels from intracellular compartments in atrial myocytes
Hannah E. Boycott, Camille S. M. Barbier, Catherine A. Eichel, Kevin D. Costa, Raphael P. Martins, Florent Louault, Gilles DilanianAlain Coulombe, Stéphane N. Hatem and Elise Balse
Proceedings of the National Academy of Sciences (PNAS) E3955–E3964, 2013
doi: 10.1073/pnas.1309896110
[See also this video]

Dynamic of Ion Channel Expression at the Plasma Membrane of Cardiomyocytes
Balse E, Steele DF, Abriel H, Coulombe A, Fedida D, Hatem SN
Physiol Rev 92: 1317-1358, 2012
doi:10.1152/physrev.00029.2011

SAP97 and Dystrophin Macromolecular Complexes Determine Two Pools of Cardiac Sodium Channels Na(v)1.5 in Cardiomyocytes
Petitprez, S, Zmoos, AF, Ogrodnik, J, Balse, E, Raad, N, El-Haou, S, Albesa, M, Bittihn, P, Luther, S, Lehnart, SE, Hatem, SN, Coulombe, A, Abriel, H, AF Petitprez, Severine, Zmoos, Anne-Flore, Ogrodnik, Jakob,, Balse, Elise, Raad, Nour, El-Haou, Said, Albesa, Maxime, Bittihn, Philip, Luther, Stefan, Lehnart, Stephan E., Hatem, Stephane N., Coulombe, Alain, Abriel, Hugues
Circulation Research 2011; 108: 294-304
doi: 10.1161/CIRCRESAHA.110.228312