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Arachidonic Acid Hyperpolarizes Mesenchymal Stromal Cells From the Human Adipose Tissue by Stimulating TREK1 K

Michail V Tarasov, Polina D Kotova, Marina F Bystrova, Natalia V Kabanova, Veronika Yu Sysoeva, Stanislav S Kolesnikov

Channels (Austin). 2019 Dec;13(1):36-47.

PMID: 30661462

Abstract:

The current knowledge of electrogenesis in mesenchymal stromal cells (MSCs) remains scarce. Earlier, we demonstrated that in MSCs from the human adipose tissue, transduction of certain agonists involved the phosphoinositide cascade. Its pivotal effector PLC generates DAG that can regulate ion channels directly or via its derivatives, including arachidonic acid (AA). Here we showed that AA strongly hyperpolarized MSCs by stimulating instantly activating, outwardly rectifying TEA-insensitive K+ channels. Among AA-regulated K+ channels, K2P channels from the TREK subfamily appeared to be an appropriate target. The expression of K2P channels in MSCs was verified by RT-PCR, which revealed TWIK-1, TREK-1, and TASK-5 transcripts. The TREK-1 inhibitor spadin antagonized the electrogenic action of AA, which was simulated by the channel activator BL 1249. This functional evidence suggested that TREK-1 channels mediated AA-dependent hyperpolarization of MSCs. Being mostly silent at rest, TREK-1 negligibly contributed to the "background" K+ current. The dramatic stimulation of TREK-1 channels by AA indicates their involvement in AA-dependent signaling in MSCs.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP18200130 BL-1249 BL-1249 18200-13-0 Price
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