The TRPV2 channel mediates Ca2+ influx and the Δ9-THC-dependent decrease in osmotic fragility in red blood cells

Abstract

Not available.

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

“…The discovery of the TRPV2 in RBCs is a remarkable finding because the abundance of ion channel copies is very low in the RBC membrane and functional channel recordings are complicated to align with molecular identities (Kaestner, 2015). Even in the study, where the TRPV2 was found, the detection of the Gárdos channel (KCNN4, K Ca 3.1, hSK4) was below the quality threshold in the proteomic study (Belkacemi et al, 2021).…”

“…We like to discuss two particular outcomes in more detail that may be relevant for the understanding of RBC physiology. A key point of the report by Belkacemi et al (2021) was an increase of the osmotic fragility in TRPV2 KO mouse RBCs. The conclusion drawn is that TRPV2 mediated Ca 2+ entry activates the Gárdos channel followed by K + loss and subsequent loss of water, similar to what has already been suggested for PIEZO1.…”

“…Very recently the transient receptor potential vanilloid type 2 (TRPV2) channel was reported to be present in RBCs (Belkacemi et al, 2021 ). TRPV2 is a non-selective cation channel conducting also Ca 2+ and can be activated by Δ9-tetrahydrocannabinol (Δ9-THC) or cannabidiol (CBD).…”

“…In their paper (Belkacemi et al, 2021 ) showed that osmotic fragility is decreased upon RBC stimulation with Δ9-THC with Ca 2+ being present in the external solution, that could partly be reversed by the additional application of the Gárdos channel inhibitor TRAM34. However, if RBCs are exposed to hypoosmotic conditions as performed in the paper, the cell swelling is expected to activate PIEZO1 or other mechanosensitive channels that mediate Ca 2+ influx (Danielczok et al, 2017 ) i.e., one would expect a Gárdos channel-dependent modulation of the osmotic fragility since internal Ca 2+ should increase, mediated by mechanosensitive cation channel activity.…”

“…Such a behavior echoes a recent report of an unrecognized non-selective cation channel in human RBCs activated upon extracellular Ca 2+ depletion and thought to potentially be a non-negligible part of the leaky pathways that contribute to the cation gradients dissipation upon storage with Ca 2+ depleted solutions (Petkova-Kirova et al, 2018 ). To illustrate the similarity in functional behavior, we compiled Figures 1A–C to compare the I-V behavior of TRPV2 as described by Belkacemi et al ( 2021 ) and the non-selective cation channel reported by Petkova-Kirova et al ( 2018 ). When comparing the I-V relationship one should keep in mind the different recording conditions in two different laboratories.…”