0215 : Is Transient Receptor Potential Vanilloid Type 1 (TRPV1) a target of isoflurane in cardiomyocytes?

During a myocardial infarct, oxygen and nutrients deprivation triggers a reticular stress disrupting the Ca2+ balance of the cardiac cell. Several Ca2+ pumps and channels located at the sarcolemma or at the reticulum membrane are key players in this maintenance of Ca2+ homeostasis. Among them, we find passive leak channels, such as TRPs. Their involvement in myocardial ischemia-reperfusion injury has gained recognition recently, but the underlying mechanisms are not yet well understood. TRPV1 represents a non-selective cation channel that is activated by capsaicin, pH and high temperature. In skeletal muscle, we recently demonstrated that TRPV1 is located in the longitudinal part of the SR and respond to pharmacological and physiological activations (Lotteau et al., 2013). We questioned here whether TRPV1 might have a role in heart physiology. Biochemical analysis and intracellular Ca2+ measurements were performed on cardiomyocytes from wild-type and TRPV1-KO mice. Our in vitro results show that: (i) TRPV1 is expressed in cardiac cells; (ii) an increase in intracellular calcium concentration ([Ca2+]i) is elicited under TRPV1 activation; (iii) TRPV1 could be a direct target of isoflurane. In parallel, our in vivo results indicate that a pharmacological preconditioning by isoflurane decrease the infarct size, probably though activation of TRPV1. Ca2+ is central for the heart function, through its physiological role in excitation- contraction coupling, and the detrimental impact of Ca2+ overload during myocardial ischemia-reperfusion. It appears crucial to clarify the role of calcium leak channels such as TRPV1 channels in regulating Ca2+ homeostasis. According to the fact that TRPV1 activity can be modulated by a lot of pharmacological molecules, TRPV1 may serve as therapeutic target to reduce the infarct size. The author hereby declares no conflict of interest