The Transient Receptor Potential Vanilloid Type 2 (TRPV2) Channel–A New Druggable Ca2+ Pathway in Red Cells, Implications for Red Cell Ion Homeostasis

Egée, Stéphane; Kaestner, Lars

doi:10.3389/fphys.2021.677573

Cited by 15 publications

(13 citation statements)

References 39 publications

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“…When the authors activated TRPV2 by channel agonists (cannabidiol and Δ9-tetrahydrocannabinol), they observed cell swelling and that the occurrence of stomatocytes and spherocytes increased and discocytes significantly decreased (Belkacemi et al, 2021 ). Although there are no data on the mechanical activation of TRPV2 in RBCs, Egee and Kaestner hypothesized that a strong activation of TRPV2 could lead to cell swelling by an increase in the intracellular Na + concentration, which exceeds the K + efflux (Egee and Kaestner, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

A Novel Fragmentation Sensitivity Index Determines the Susceptibility of Red Blood Cells to Mechanical Trauma

et al. 2021

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Supraphysiological shear stresses (SSs) induce irreversible impairments of red blood cell (RBC) deformability, overstretching of RBC membrane, or fragmentation of RBCs that causes free hemoglobin to be released into plasma, which may lead to anemia. The magnitude and exposure tisme of the SSs are two critical parameters that determine the hemolytic threshold of a healthy RBC. However, impairments in the membrane stability of damaged cells reduce the hemolytic threshold and increase the susceptibility of the cell membrane to supraphysiological SSs, leading to cell fragmentation. The severity of the RBC fragmentation as a response to the mechanical damage and the critical SS levels causing fragmentation are not previously defined. In this study, we investigated the RBC mechanical damage in oxidative stress (OS) and metabolic depletion (MD) models by applying supraphysiological SSs up to 100 Pa by an ektacytometer (LORRCA MaxSis) and then assessed RBC deformability. Next, we examined hemolysis and measured RBC volume and count by Multisizer 3 Coulter Counter to evaluate RBC fragmentation. RBC deformability was significantly impaired in the range of 20–50 Pa in OS compared with healthy controls (p < 0.05). Hemolysis was detected at 90–100 Pa SS levels in MD and all applied SS levels in OS. Supraphysiological SSs increased RBC volume in both the damage models and the control group. The number of fragmented cells increased at 100 Pa SS in the control and MD and at all SS levels in OS, which was accompanied by hemolysis. Fragmentation sensitivity index increased at 50–100 Pa SS in the control, 100 Pa SS in MD, and at all SS levels in OS. Therefore, we propose RBC fragmentation as a novel sensitivity index for damaged RBCs experiencing a mechanical trauma before they undergo fragmentation. Our approach for the assessment of mechanical risk sensitivity by RBC fragmentation could facilitate the close monitoring of shear-mediated RBC response and provide an effective and accurate method for detecting RBC damage in mechanical circulatory assist devices used in routine clinical procedures.

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Section: Discussionmentioning

confidence: 99%

A Novel Fragmentation Sensitivity Index Determines the Susceptibility of Red Blood Cells to Mechanical Trauma

et al. 2021

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“…The abundance of the transient receptor potential channel vanilloid type 2 (TRPV2) in red blood cells (RBCs) was recently discovered, 1 inciting immediate discussion on its potential physiological importance. 2 TRPV2 is a reportedly mechanosensitive nonselective cation channel with numerous properties similar to those of Piezo1. 2 It has been proposed that TRPV2 may cause the induction of storage lesions in RBCs.…”

Section: Transient Receptor Potential Channel Vanilloid Type 2 In Red...mentioning

confidence: 99%

“…2 TRPV2 is a reportedly mechanosensitive nonselective cation channel with numerous properties similar to those of Piezo1. 2 It has been proposed that TRPV2 may cause the induction of storage lesions in RBCs. 2,3 Furthermore, TRPV2 channels can be activated by cannabidiol or Δ9-tetrahydrocannabinol (Δ9-THC) and vice versa; thus, the changes induced in RBC by the application of Δ9-THC can be attributed to TRPV2 channel activity, which was first reported in RBCs of TRPV2-KO mice.…”

Section: Transient Receptor Potential Channel Vanilloid Type 2 In Red...mentioning

confidence: 99%

“…2 It has been proposed that TRPV2 may cause the induction of storage lesions in RBCs. 2,3 Furthermore, TRPV2 channels can be activated by cannabidiol or Δ9-tetrahydrocannabinol (Δ9-THC) and vice versa; thus, the changes induced in RBC by the application of Δ9-THC can be attributed to TRPV2 channel activity, which was first reported in RBCs of TRPV2-KO mice. 1 Figure 1A,B shows confocal images of the RBCs of a 29-year-old man who participated in an initial study.…”

Section: Transient Receptor Potential Channel Vanilloid Type 2 In Red...mentioning

confidence: 99%

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Transient receptor potential channel vanilloid type 2 in red cells of cannabis consumer

et al. 2022

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“…Therefore, most of the information available today is scattered, contradictory and does not permit the reconstruction of the whole jigsaw puzzle that would reveal the role of ion channels in the function of the RBCs. This holds true, especially in the context that ion channels in RBCs are still being discovered, like the transient receptor potential channel TRPV2 (Belkacemi et al, 2021;Egee and Kaestner, 2021) suggesting that further ion channels can be discovered, or new electrophysiological effects like "pseudo action potentials, " which are found in RBCs (Jansen et al, 2021) and awaiting their full physiological explanation.…”

Section: Introductionmentioning

confidence: 99%

The Function of Ion Channels and Membrane Potential in Red Blood Cells: Toward a Systematic Analysis of the Erythroid Channelome

et al. 2022

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Erythrocytes represent at least 60% of all cells in the human body. During circulation, they experience a huge variety of physical and chemical stimulations, such as pressure, shear stress, hormones or osmolarity changes. These signals are translated into cellular responses through ion channels that modulate erythrocyte function. Ion channels in erythrocytes are only recently recognized as utmost important players in physiology and pathophysiology. Despite this awareness, their signaling, interactions and concerted regulation, such as the generation and effects of “pseudo action potentials”, remain elusive. We propose a systematic, conjoined approach using molecular biology, in vitro erythropoiesis, state-of-the-art electrophysiological techniques, and channelopathy patient samples to decipher the role of ion channel functions in health and disease. We need to overcome challenges such as the heterogeneity of the cell population (120 days lifespan without protein renewal) or the access to large cohorts of patients. Thereto we will use genetic manipulation of progenitors, cell differentiation into erythrocytes, and statistically efficient electrophysiological recordings of ion channel activity.

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The Transient Receptor Potential Vanilloid Type 2 (TRPV2) Channel–A New Druggable Ca2+ Pathway in Red Cells, Implications for Red Cell Ion Homeostasis

Cited by 15 publications

References 39 publications

A Novel Fragmentation Sensitivity Index Determines the Susceptibility of Red Blood Cells to Mechanical Trauma

A Novel Fragmentation Sensitivity Index Determines the Susceptibility of Red Blood Cells to Mechanical Trauma

Transient receptor potential channel vanilloid type 2 in red cells of cannabis consumer

The Function of Ion Channels and Membrane Potential in Red Blood Cells: Toward a Systematic Analysis of the Erythroid Channelome

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