Abstract 326: TRPV2 Regulates Cardiomyocyte Function via Altering Ca2+ Cycling
TRPV2 is a member of transient receptor potential vanilloid (TRPV) family. As a Ca2+ channel, it can detect various stimuli such as noxious heat (>52°C), membrane stretching, as well as a number of exogenous chemicals, including probenecid, 2-aminoethoxydiphenyl borate, and lysophospholipids. TRPV2 has been found in many tissue types, including neuron and kidney, but the function of TRPV2 in the heart is poorly understood. Here we show TRPV2 is involved in the Ca2+ cycling process and then regulates the function of the cardiomyocyte.
We identified the mRNA expression of TRPV2 in the cardiac tissues of mice using real-time PCR. By performing echocardiography we found that administration of probenecid, a selective TRPV2 agonist, increased cardiac ejection fraction in mice. This positive inotropic effect of probenecid was also shown in Langendorff perfused mice hearts as increased peak +dP/dt. In isolated ventricular myocytes, we found that probenecid significantly increased myocyte fractional shortening in a dose-dependent manner, which was fully blocked by ruthenium red, a non-selective TRPV2 blocker. We also performed fluorescent studies to examine myocyte Ca2+ cycling. We found that probenecid significantly increased Ca2+ transient and resting-state Ca2+ sparks and this effect was eliminated by ruthenium red. When Ca2+ storage in sarcoplasmic reticulum (SR) was depleted with caffeine, and SR Ca2+ reuptake was blocked by thapsigargin at the same time, probenecid did not show any effects in either Ca2+ transient or Ca2+ sparks. Our patch clamp experiments indicate that probenecid treatment does not trigger any significant transmembrane Ca2+ influx. These results point to the important role of TRPV2 in regulating SR Ca2+ release.
In conclusion, TRPV2 activation may contribute to increased SR Ca2+ release, leading to the enhancement of myocyte contractility. Thus, TRPV2 plays a potentially important role in controlling the cellular function of heart.
- © 2012 by American Heart Association, Inc.