scholarly journals TRPV4 increases cardiomyocyte calcium cycling and contractility yet contributes to damage in the aged heart following hypoosmotic stress

2018 ◽  
Vol 115 (1) ◽  
pp. 46-56 ◽  
Author(s):  
John L Jones ◽  
Deborah Peana ◽  
Adam B Veteto ◽  
Michelle D Lambert ◽  
Zahra Nourian ◽  
...  
Keyword(s):  
Protein Expression ◽  
Transient Receptor Potential ◽  
Pathological Condition ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Transient Receptor Potential Vanilloid ◽  
Aged Mice ◽  
Increased Risk ◽  
Hypoosmotic Stress

Abstract Aims Cardiomyocyte Ca2+ homeostasis is altered with aging via poorly-understood mechanisms. The Transient Receptor Potential Vanilloid 4 (TRPV4) ion channel is an osmotically-activated Ca2+ channel, and there is limited information on the role of TRPV4 in cardiomyocytes. Our data show that TRPV4 protein expression increases in cardiomyocytes of the aged heart. The objective of this study was to examine the role of TRPV4 in cardiomyocyte Ca2+ homeostasis following hypoosmotic stress and to assess the contribution of TRPV4 to cardiac contractility and tissue damage following ischaemia–reperfusion (I/R), a pathological condition associated with cardiomyocyte osmotic stress. Methods and results TRPV4 protein expression increased in cardiomyocytes of Aged (24–27 months) mice compared with Young (3–6 months) mice. Immunohistochemistry revealed TRPV4 localization to microtubules and the t-tubule network of cardiomyocytes of Aged mice, as well as in left ventricular myocardium of elderly patients undergoing surgical aortic valve replacement for aortic stenosis. Following hypoosmotic stress, cardiomyocytes of Aged, but not Young exhibited an increase in action-potential induced Ca2+ transients. This effect was mediated via increased sarcoplasmic reticulum Ca2+ content and facilitation of Ryanodine Receptor Ca2+ release and was prevented by TRPV4 antagonism (1 μmol/L HC067047). A similar hypoosmotic stress-induced facilitation of Ca2+ transients was observed in Young transgenic mice with inducible TRPV4 expression in cardiomyocytes. Following I/R, isolated hearts of Young mice with transgenic TRPV4 expression exhibited enhanced contractility vs. hearts of Young control mice. Similarly, hearts of Aged mice exhibited enhanced contractility vs. hearts of Aged TRPV4 knock-out (TRPV4−/−) mice. In Aged, pharmacological inhibition of TRPV4 (1 μmol/L, HC067047) prevented hypoosmotic stress-induced cardiomyocyte death and I/R-induced cardiac damage. Conclusions Our findings provide a new mechanism for hypoosmotic stress-induced cardiomyocyte Ca2+ entry and cell damage in the aged heart. These finding have potential implications in treatment of elderly populations at increased risk of myocardial infarction and I/R injury.

Contribution of TRPV4 to enhanced calcium cycling and cardiac arrhythmia following ischemia-reperfusion in aged mouse hearts

2020 ◽  
Author(s):  
◽  
Deborah Peana
Keyword(s):  
Transient Receptor Potential ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Calcium Handling ◽  
Transient Receptor Potential Vanilloid ◽  
Aged Mouse ◽  
Aged Mice ◽  
Hypoosmotic Stress ◽  
Perfused Hearts ◽  
Young Mice

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI--COLUMBIA AT REQUEST OF AUTHOR.] Cardiomyocyte Ca2+ homeostasis is altered with aging and predisposes the Aged heart to Ca2+ intolerance and arrhythmia. Transient Receptor Potential Vanilloid 4 (TRPV4) is an osmotically-activated cation channel and channel expression is increased in cardiomyocytes of Aged mice. The central goal of this work was to determine the role of TRPV4 in calcium handling and arrhythmogenesis in response to hypoosmotic stress and following ischemia-reperfusion (I/R). Hypoosmotic stress induced an increase in calcium transient amplitude in cardiomyocytes isolated from Aged mice which was followed by an increased incidence of arrhythmic Ca2+ events and Ca2+ waves. This effect was prevented by TRPV4 inhibition and was absent in cardiomyocytes from Young mice. Cardiac contractile function, membrane potential, and cardiac ECG was monitored in Langendorff-perfused hearts during I/R. Aged hearts responded to I/R with an initial increase in contractile function, membrane depolarization, and incidence of ventricular arrhythmia during reperfusion. This effect was attenuated by TRPV4 inhibition and was absent in hearts of Young mice. Also, in hearts of Aged, TRPV4 inhibition decreased the percent of damaged tissue following I/R compared to untreated conditions. Finally, Langendorff-perfused hearts from Aged mice expressing a genetically encoded Ca2+ sensor (GCaMP6f) were subjected to I/R and demonstrated an increased Ca2+ transient amplitude and incidence of arrhythmic Ca2+ waves compared to Aged mice treated with TRPV4 inhibition. These findings suggest that TRPV4 may contribute to initial inotropy followed by pro-arrhythmic cardiomyocyte Ca2+ signaling, arrhythmogenesis, and cell death following I/R in the Aged heart.

Myocardial Noncompaction

2018 ◽  
Vol 69 (8) ◽  
pp. 2209-2212
Author(s):  
Alexandru Radu Mihailovici ◽  
Vlad Padureanu ◽  
Carmen Valeria Albu ◽  
Venera Cristina Dinescu ◽  
Mihai Cristian Pirlog ◽  
...  
Keyword(s):  
Ventricular Arrhythmias ◽  
Specific Treatment ◽  
Left Ventricular ◽  
Left Ventricular Noncompaction ◽  
Ventricular Noncompaction ◽  
Genetic Transmission ◽  
Asymptomatic Patients ◽  
Increased Risk ◽  
Patients With Heart Failure

Left ventricular noncompaction is a primary cardiomyopathy with genetic transmission in the vast majority of autosomal dominant cases. It is characterized by the presence of excessive myocardial trabecularities that generally affect the left ventricle. In diagnosing this condition, echocardiography is the gold standard, although this method involves an increased risk of overdiagnosis and underdiagnosis. There are also uncertain cases where echocardiography is inconclusive, a multimodal approach is needed, correlating echocardiographic results with those obtained by magnetic resonance imaging. The clinical picture may range from asymptomatic patients to patients with heart failure, supraventricular or ventricular arrhythmias, thromboembolic events and even sudden cardiac death. There is no specific treatment of left ventricular noncompaction, but the treatment is aimed at preventing and treating the complications of the disease. We will present the case of a young patient with left ventricular noncompactioncardiomyopathy and highlight the essential role of transthoracic echocardiography in diagnosing this rare heart disease.

scholarly journals Interactions between Chemesthesis and Taste: Role of TRPA1 and TRPV1

2021 ◽  
Vol 22 (7) ◽  
pp. 3360
Author(s):  
Mee-Ra Rhyu ◽  
Yiseul Kim ◽  
Vijay Lyall
Keyword(s):  
Transient Receptor Potential ◽  
Taste Receptor ◽  
Sensory Nerve ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channels ◽  
Trigeminal Neurons ◽  
Calcitonin Gene ◽  
Transient Receptor

In addition to the sense of taste and olfaction, chemesthesis, the sensation of irritation, pungency, cooling, warmth, or burning elicited by spices and herbs, plays a central role in food consumption. Many plant-derived molecules demonstrate their chemesthetic properties via the opening of transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels. TRPA1 and TRPV1 are structurally related thermosensitive cation channels and are often co-expressed in sensory nerve endings. TRPA1 and TRPV1 can also indirectly influence some, but not all, primary taste qualities via the release of substance P and calcitonin gene-related peptide (CGRP) from trigeminal neurons and their subsequent effects on CGRP receptor expressed in Type III taste receptor cells. Here, we will review the effect of some chemesthetic agonists of TRPA1 and TRPV1 and their influence on bitter, sour, and salt taste qualities.

scholarly journals Transient Receptor Potential Vanilloid in the Brain Gliovascular Unit: Prospective Targets in Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 334
Author(s):  
Huilong Luo ◽  
Xavier Declèves ◽  
Salvatore Cisternino
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Brain Diseases ◽  
Transient Receptor Potential Vanilloid ◽  
Main Role ◽  
Trpv Channels ◽  
Gliovascular Unit ◽  
Transient Receptor ◽  
The Brain

The gliovascular unit (GVU) is composed of the brain microvascular endothelial cells forming blood–brain barrier and the neighboring surrounding “mural” cells (e.g., pericytes) and astrocytes. Modulation of the GVU/BBB features could be observed in a variety of vascular, immunologic, neuro-psychiatric diseases, and cancers, which can disrupt the brain homeostasis. Ca2+ dynamics have been regarded as a major factor in determining BBB/GVU properties, and previous studies have demonstrated the role of transient receptor potential vanilloid (TRPV) channels in modulating Ca2+ and BBB/GVU properties. The physiological role of thermosensitive TRPV channels in the BBB/GVU, as well as their possible therapeutic potential as targets in treating brain diseases via preserving the BBB are reviewed. TRPV2 and TRPV4 are the most abundant isoforms in the human BBB, and TRPV2 was evidenced to play a main role in regulating human BBB integrity. Interspecies differences in TRPV2 and TRPV4 BBB expression complicate further preclinical validation. More studies are still needed to better establish the physiopathological TRPV roles such as in astrocytes, vascular smooth muscle cells, and pericytes. The effect of the chronic TRPV modulation should also deserve further studies to evaluate their benefit and innocuity in vivo.

Intra-arterial instillation of a nociceptive agent modulate cardiorespiratory parameters involving 5-HT3 and TRPV1 receptors in anesthetized rats

2021 ◽  
Vol 21 ◽  
Author(s):  
Sanjeev K. Singh ◽  
M. S. Muthu ◽  
Ravindran Revand ◽  
M. B. Mandal
Keyword(s):  
Transient Receptor Potential ◽  
Sensory Nerve ◽  
Receptor Potential ◽  
Neural Mechanisms ◽  
Transient Receptor Potential Vanilloid ◽  
Anesthetized Rats ◽  
Trpv1 Receptors ◽  
Perivascular Nerves ◽  
Transient Receptor

Background: Since long back, it has been a matter of discussion regarding the role of peripheral blood vessels in regulation of cardiorespiratory (CVR) system. Objective: The role of 5-HT3 and TRPV1 receptors present on perivascular nerves in elicitation of CVR reflexes was examined after intra-arterial instillation of bradykinin in urethane anesthetized rats. Materials and Methods: Femoral artery was cannulated retrogradely and was utilized for the instillation of saline/agonist/antagonist and recording of blood pressure (BP), using a double ported 24G cannula. BP, respiration and ECG were recorded for 30 min after bradykinin (1 µM) in the absence or presence of antagonists. Results: Instillation of bradykinin produced immediate hypotensive (40%), bradycardiac (17%), tachypnoeic (45%) and hyperventilatory (96%) responses of shorter latencies (5-8 s) favoring the neural mechanisms in producing the responses. In lignocaine (2%) pretreated animals, bradykinin-induced hypotensive (10%), bradycardiac (1.7%), tachypnoeic (13%) and hyperventilatory (13%) responses attenuated significantly. Pretreatment with ondansetron (100 µg/kg), 5-HT3-antagonist attenuated the hypotensive (10%), bradycardiac (1.7%), tachypnoeic (11%) and hyperventilatory (11%) responses significantly. Pretreatment with capsazepine (1 mg/kg), transient receptor potential vanilloid 1- antagonist blocked the hypotensive (5%), bradycardiac (1.2%), tachypnoeic (6%) and hyperventilatory (6%) responses significantly. Conclusion: In conclusion, presence of a nociceptive agent in the local segment of an artery evokes vasosensory reflex responses modulating CVR parameters involving TRPV1 and 5-HT3 receptors present on the perivascular sensory nerve terminals in anesthetized rats.

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