title: Novel role of transient receptor potential vanilloid 2 in the regulation of cardiac performance.
abstract: Transient receptor potential cation channels have been implicated in the regulation of cardiovascular function, but only recently has our laboratory described the vanilloid-2 subtype (TRPV2) in the cardiomyocyte, though its exact mechanism of action has not yet been established. This study tests the hypothesis that TRPV2 plays an important role in regulating myocyte contractility under physiological conditions. Therefore, we measured cardiac and vascular function in wild-type and TRPV2(-/-) mice in vitro and in vivo and found that TRPV2 deletion resulted in a decrease in basal systolic and diastolic function without affecting loading conditions or vascular tone. TRPV2 stimulation with probenecid, a relatively selective TRPV2 agonist, caused an increase in both inotropy and lusitropy in wild-type mice that was blunted in TRPV2(-/-) mice. We examined the mechanism of TRPV2 inotropy/lusitropy in isolated myocytes and found that it modulates Ca(2+) transients and sarcoplasmic reticulum Ca(2+) loading. We show that the activity of this channel is necessary for normal cardiac function and that there is increased contractility in response to agonism of TRPV2 with probenecid.
authors: Division of Cardiovascular Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio;
authors: Jack
authors: J
authors: Rubinstein
authors: Valerie M
authors: VM
authors: Lasko
authors: Sheryl E
authors: SE
authors: Koch
authors: Vivek P
authors: VP
authors: Singh
authors: Vinicius
authors: V
authors: Carreira
authors: Nathan
authors: N
authors: Robbins
authors: Amit R
authors: AR
authors: Patel
authors: Min
authors: M
authors: Jiang
authors: Philip
authors: P
authors: Bidwell
authors: Evangelia G
authors: EG
authors: Kranias
authors: W Keith
authors: WK
authors: Jones
authors: John N
authors: JN
authors: Lorenz
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D011339:Probenecid / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D014528:Uricosuric Agents / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D050916:TRPV Cation Channels; C485717:Trpv2 protein, mouse; D014528:Uricosuric Agents; D011339:Probenecid
keywords: blood flow; blood pressure; calcium; cardiac myocytes; contractility; hemodynamics; ion channels; probenecid; vascular resistance