For multiple approaches, ranging from whole animal to isolated cell, we seek to determine the role of TRPM4 in cardiovascular physiology through a tool of mice disabled for the gene coding TRPM4. Thus, we have recently shown that the absence of the channel during cardiac development induces an increase in the number of ventricular cardiomyocytes, which results in an enlargement in the adult mouse. In addition, the absence of the channel in adults results in cardiac conduction disorders. Finally, it would intervene directly on the duration of the atrial action potential increasing its duration.
TRPM4 is nonselective cation channel activated by intracellular calcium whose expression is ubiquitous (immune system, beta cells of the pancreas, brain arteries …). However, at the heart level, its presence is differentially expressed according to heart territories, and it is distributed in the sinus node and atria, conduction tissue. In humans, mutations of this channel have been shown to be responsible for conduction disturbances and Brugada syndrome. Furthermore, TRPM4 be involved in regulating sinus rhythm.
The techniques used range from in vivo (echocardiography, telemetry) at the cellular level (calcium imaging, electrophysiology) passing by immunofluorescence analysis cryo-cuts, biochemistry, molecular biology
- Pierre Launay (UMR1149, Paris),
- Patrice Bouvagnet (Université de Lyon).
Major Publications :
- Guinamard R, Demion M, Launay P. Physiological roles of the TRPM4 channel extracted from background currents.. Physiology. 2010.
- Demion M, Thireau J, Gueffier M, Finan A, Khoueiry Z, Cassan C, Serafini N, Aimond F, Granier M, Pasquié JL, Launay P, Richard S. (2014). “Trpm4 gene invalidation leads to cardiac hypertrophy and electrophysiological alterations. “ PLoS One. 22;9(12):e115256.