TRPV4 contributes to stretch-induced hypercontractility and time-dependent dysfunction in the aged heart

2019 ◽  
Author(s):  
◽  
Adam Bruce Veteto
Keyword(s):  
Cardiovascular Disease ◽  
Cardiac Function ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Time Dependent ◽  
Calcium Handling ◽  
Transient Receptor Potential Vanilloid ◽  
University Of Missouri ◽  
Transient Receptor ◽  
The University

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Aims: Cardiovascular disease remains the greatest cause of mortality in Americans over 65. The stretch-activated Transient Receptor Potential Vanilloid-4 (TRPV4) ion channel is expressed in cardiomyocytes of the aged heart. This investigation tests the hypothesis that TRPV4 alters calcium handling and cardiac function in response to increased ventricular preload and cardiomyocyte stretch.

Abstract 358: Transient Receptor Potential Vanilloid 2 (TRPV2) contributes to myocardial contractility and hypertrophy via sarcoplasmic reticulum calcium handling

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Jack Rubinstein ◽  
Vivek P Singh ◽  
Valerie M Lasko ◽  
Sheryl E Koch ◽  
Evangelia Kranias ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Fold Increase ◽  
Calcium Handling ◽  
Heart Weight ◽  
Transient Receptor Potential Vanilloid ◽  
Cardiomyocyte Contractility ◽  
Transient Receptor

Background: TRPV2 is a Ca2+ channel that we have recently discovered in cardiomyocytes. The absence of this channel negatively impacts baseline contractility while stimulation results in a positive inotropic response. What remains to be established is the mechanism of this receptor and its role, if any, in the development of hypertrophy. Methods and Results: We obtained isolated cardiomyocytes from wild type (WT) and TRPV2-/- (KO) mice and found that the sarcoplasmic reticulum Ca2+ content and Ca2+ transients were reduced along with fractional shortening in the KO cardiomyocytes (figure, panels A, B, C). In vivo echocardiography confirmed a decrease in ejection fraction in KO mice in comparison to the WT counterparts (panel D). The relevance of these findings was examined in 6 WT and 5 KO mice subjected to transverse aortic constriction (TAC). These mice were followed by echocardiography weekly for a total of 8 weeks post TAC. At the conclusion, the hearts were obtained for histological and molecular analyses. We demonstrated that the KO mice developed less LV hypertrophy in comparison to WT (via echocardiography and by heart weight/body weight ratios) (figure, panels E and F). Importantly, there was a 5 fold increase in TRPV2 expression assessed by PCR in TAC WT hearts, compared to WT not subjected to TAC (0.72±0.10 vs. 0.13±0.04; p<0.01). This suggests a role for TRPV2 not only in contractility, but also in the development of hypertrophy. Conclusions: We have discovered a novel cardiac channel that alters Ca2+ cycling and is capable of modulating cardiomyocyte contractility and hypertrophy, which could lead to novel therapeutic options in heart failure and hypertrophy.

Segmental transport of Ca2+ and Mg2+ along the gastrointestinal tract

2015 ◽  
Vol 308 (3) ◽  
pp. G206-G216 ◽  
Author(s):  
Anke L. Lameris ◽  
Pasi I. Nevalainen ◽  
Daphne Reijnen ◽  
Ellen Simons ◽  
Jelle Eygensteyn ◽  
...  
Keyword(s):  
Vitamin D ◽  
Gastrointestinal Tract ◽  
Intestinal Absorption ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
The Body ◽  
Time Dependent ◽  
Transient Receptor Potential Vanilloid ◽  
Dependent Manner ◽  
Transient Receptor

Calcium (Ca2+) and magnesium (Mg2+) ions are involved in many vital physiological functions. Since dietary intake is the only source of minerals for the body, intestinal absorption is essential for normal homeostatic levels. The aim of this study was to characterize the absorption of Ca2+ as well as Mg2+ along the gastrointestinal tract at a molecular and functional level. In both humans and mice the Ca2+ channel transient receptor potential vanilloid subtype 6 (TRPV6) is expressed in the proximal intestinal segments, whereas Mg2+ channel transient receptor potential melastatin subtype 6 (TRPM6) is expressed in the distal parts of the intestine. A method was established to measure the rate of Mg2+ absorption from the intestine in a time-dependent manner by use of 25Mg2+. In addition, local absorption of Ca2+ and Mg2+ in different segments of the intestine of mice was determined by using surgically implanted intestinal cannulas. By these methods, it was demonstrated that intestinal absorption of Mg2+ is regulated by dietary needs in a vitamin D-independent manner. Also, it was shown that at low luminal concentrations, favoring transcellular absorption, Ca2+ transport mainly takes place in the proximal segments of the intestine, whereas Mg2+ absorption predominantly occurs in the distal part of the gastrointestinal tract. Vitamin D treatment of mice increased serum Mg2+ levels and 24-h urinary Mg2+ excretion, but not intestinal absorption of 25Mg2+. Segmental cannulation of the intestine and time-dependent absorption studies using 25Mg2+ provide new ways to study intestinal Mg2+ absorption.

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