Role of transient receptor potential vanilloid 2 in exercise tolerance and cardiac function (545.5)

Background: We have previously shown that abrogation of the semi‐selective calcium channel Transient Receptor Potential Vanilloid 2 (TRPV2) results in impaired cardiac contractility without any other observable phenotype. To expand on these findings, we investigated the effect of TRPV2 abrogation on exercise tolerance and corresponding changes in cardiac function. Methods: A group of 8‐12 week male WT and TRPV2 ‐/‐ mice were subjected to 4 weeks of daily treadmill exercise with weekly endurance training. A second group underwent 4 weeks of voluntary wheel running. Interruptions in treadmill exercise and voluntary running distances were assessed in addition to weekly echocardiographic imaging. Results: TRPV2 abrogation resulted in decreased tolerance to treadmill exercise (p<0.05 versus WT). Echocardiographic imaging showed that cardiac functional parameters improved in WT mice but not in TRPV2 ‐/‐ (treadmill) mice in response to exercise as measured by EF, SV, and CO (p<0.05 vs. baseline and in comparison to WT). Ongoing wheel experiments have preliminarily demonstrated a similar pattern. Conclusions: TRPV2 abrogation results in impaired cardiac function, exercise tolerance and cardiac response to exercise. Associated studies are underway to elucidate the underlying mechanisms involved.