Arachidonic acid hyperpolarizes mesenchymal stromal cells from the human adipose tissue by stimulating TREK1 K⁺ channels

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.

Polythiophene-mediated light modulation of membrane potential and calcium signalling in human adipose-derived stem/stromal cells

“…30 Furthermore, in endothelial cell models a similar effect was attributed to spatially-confined modulation of the transient receptor potential (TRP) vanilloid channel TRPV1, as mainly due to a photoelectrochemical process. 33,42 Interestingly, pH and temperature dependent channels, including canonical TRP (TRPC), melastatin TRP (TRPM), and tandem pore-class K + (TREK) channels, are also expressed in hASC, and they play critical roles in differentiation, migration and proliferation, 43,44 as much as K + channels. 45 However, future ad hoc pharmacological studies would be needed to unambiguously attribute the variation in the hASC membrane potential to specific ionic channels conductivity, and to unravel any influence on cell activity.…”

TRPM2 Oxidation Activates Two Distinct Potassium Channels in Melanoma Cells through Intracellular Calcium Increase

“…Several members of the K2P channel family are insensitive to TEA but sensitive to oxidizing conditions [57][58][59]. Thus, in order to determine which ion channel(s) underlie the observed current, we transfected TASK2, TREK1, TREK2, and TALK2 channels in HEK293 cells, and tested their sensitivity to Chl-T.…”

Negative Influence by the Force: Mechanically Induced Hyperpolarization via K2P Background Potassium Channels

“…The members of the TREK subfamily are activated by arachidonic acid and other polyunsaturated fatty acids (PUFA) [30,32,33], thermosensitive in the physiological range in intact cells (but not in excised patches) [34][35][36], and TREK-1 (but not TREK-2 and TRAAK) is inhibited by spadin, the secreted peptide belonging to the neurotensin receptor 3 (NTSR3/Sortilin) system [37][38][39]. TREK channels are also robustly regulated by protein interaction partners binding to the Ct. A-Kinase Anchoring Protein 150 (AKAP150), substantially increases channel activity, and prevents further activation by mechanical and other regulatory mechanisms [40].…”