Electrophysiological analysis of ß-adrenergic regulation of cardiac Nav1.5 channel

My internship will take place at the Institut du Thorax under the supervision of Céline Marionneau, CNRS researcher, and Floriane Bibault, laboratory engineer. Research within the "Ion channels and heart disease" team focuses on phosphorylation and Nav1.5 channel complexes in the regulation of normal and pathological cardiac excitability.

 

Nav1.5, potential-dependent Na+ channels, are key regulators of cardiac excitability, and any defect in their function or regulation, in the context of hereditary or acquired cardiac pathologies, increases the risk of developing lethal arrhythmias. These channels interact with numerous partner proteins, playing a key role in regulating their function and expression under both physiological and pathological conditions.However, these multiprotein complexes remain poorly understood in native cardiac tissue.

 

The major objective of this internship will be to characterize the involvement of ß-adrenergic regulation on the INa+ sodium current of NaV1.5 channels in adult cardiomyocytes. A second objective will be to determine the role of 5 phosphorylation sites on NaV1.5, and their respective or cumulative effects in HEK 293 cells and adult cardiomyocytes on sodium current. To achieve this, various electrophysiology methods will be used during this internship, such as manual and automated patch clamp using different protocols, as well as biochemical and cell culture manipulations.