0192 : Pharmacological modulation of TRPV1, a cation leak channel in mouse cardiomyocytes

The sarcoplasmic reticulum (SR) calcium homeostasis is due to a dynamic balance between the capture of the cytosolic calcium by calcium pumps such as SERCA (Sarco Endoplasmic Reticulum Calcium ATPase) and calcium release, actively across calcium channels such as IP3 (Inositol Tri-phosphate) and ryanodine receptors, or passively via calcium leak channels. Few data are available concerning the functional characterization of leak channels in the SR. These channels are involved in the regulation of the reticular calcium concentration as well as in the exchange of calcium between SR and other intracellular organelles. Therefore, their characterization is important for a better understanding of the physiology of the cells. Recently, we have demonstrated that TRPV1 (Transient Receptor Potential Vanilloid 1), a cationic channel, is a functional calcium leak channel on the SR of mouse skeletal muscle cells. TRPV1 is activated by acidosis, high temperature (>42°C), and by pharmacological molecules such as capsaicin, resiniferatoxin and capsazepin. We are pursuing our investigation of these channels in C57Bl6 mouse cardiomyocytes. Our preliminary results show that TRPV1 is active in mice cardiomyocytes as a calcium leak channel after stimulation or inhibition using pharmacological molecules. These data were confirmed by using a genetic approach: the C57Bl6 KO mice for TRPV1 channel. Lately, reducing cardiac injuries after ischemia reperfusion where calcium dynamics play a crucial role became a major interest. Therefore, the modulation of the TRPV1 calcium leak channel might be a new approach in cardioprotection.