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Identification of TREK-2 K+ channels in human mesenchymal stromal cells

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Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

The maintenance of pluripotency of mesenchymal stromal cells (MSCs), their proliferation and initiation of differentiation may critically depend on functional expression of ion channels. Despite such a possibility, mechanisms of electrogenesis in MSCs remain poorly understood. In particular, little is known about a variety of ion channels active in resting MSCs or activated upon MSC stimulation. Here we aimed at uncovering ion channels operating in MSCs, including those being active at rest, using the patch clamp technique and inhibitory analysis. In trying to evaluate a contribution of anion channels in MSC resting potential, we employed a number of diverse inhibitors of anion channels and transporters, including niflumic acid (NFA). Basically, NFA caused hyperpolarization of MSCs that was accompanied by a marked increase in ion conductance of their plasma membranes. The blockage of Cl channels could not underlie such a NFA effect, given that cells dialyzed with a CsCl solution were weakly or negligibly sensitive to this blocker. This and other findings indicated that NFA affected the MSC ion permeability not by targeting Cl channels but by stimulating K+ channels. NFA-activated K+ current was TEA and diltiazem blockable, and K+ channels involved were potentiated from outside by solution acidification and Cu2+ ions. Taken together, the data obtained implicated two-pore domain K+ channels of the TREK-2 subtype in mediating stimulatory effects of NFA on MSCs. The notable inference from our work is that TREK-2 channels should be expressed and functional virtually in every MSC, given that all cells examined by us (n > 100) similarly responded to NFA by increasing their TREK-2-like K+ conductance.

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Correspondence to S. S. Kolesnikov.

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Original Russian Text © M.V. Tarasov, P.D. Kotova, O.A. Rogachevskaja, V.Yu. Sysoeva, S.S. Kolesnikov, 2014, published in Biologicheskie Membrany, 2014, Vol. 31, No. 3, pp. 177–184.

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Tarasov, M.V., Kotova, P.D., Rogachevskaja, O.A. et al. Identification of TREK-2 K+ channels in human mesenchymal stromal cells. Biochem. Moscow Suppl. Ser. A 8, 225–231 (2014). https://doi.org/10.1134/S1990747814020147

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  • DOI: https://doi.org/10.1134/S1990747814020147

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