Electrogenesis in mesenchymal stromal cells (MSCs) remains poorly understood. Little is known about ion channels active in resting MSCs and activated upon MSC stimulation, particularly, by agonists mobilizing Ca2+ in the MSC cytoplasm. A variety of Ca2+-gated ion channels may couple Ca2+ signals to polarization of the plasma membrane. Here, we studied MSCs from the human adipose tissue and found that in cells responsive to ATP and adenosine with Ca2+ transients or exhibiting spontaneous Ca2+ oscillations, Ca2+ bursts were associated with hyperpolarization mediated by Ca2+-gated K+ channels. The expression analysis revealed transcripts for KCNMA1 and KCNN4 genes encoding for Ca2+-activated K+ channels of large (KCa1.1) and intermediate (KCa3.1) conductance, respectively. Moreover, transcripts for the Ca2+-gated cation channel TRPM4 and anion channels Ano1, Ano2, and bestrophin-1, bestrophin-3, and bestrophin-4 were revealed. In all assayed MSCs, a rise in cytosolic Ca2+ stimulated K+ currents that were inhibited with iberiotoxin. This suggested that KCa1.1 channels are invariably expressed in MSCs. In ATP- and adenosine-responsive cells, iberiotoxin and TRAM-34 diminished electrical responses, implicating both KCa1.1 and KCa3.1 channels in coupling agonist-dependent Ca2+ signals to membrane voltage. Functional tests pointed at the existence of two separate MSC subpopulations exhibiting Ca2+-gated anion currents that were mediated by Ano2-like and bestrophin-like anion channels, respectively. Evidence for detectable activity of Ano1 and TRPM4 was not obtained. Thus, KCa1.1 channels are likely to represent the dominant type of Ca2+-activated K+ channels in MSCs, which can serve in concert with KCa3.1 channels as effectors downstream of G-protein-coupled receptor (GPCR)-mediated Ca2+ signaling.
Keywords: ATP; Adenosine; Ca2+ imaging; Ca2+-activated K+ channels; Mesenchymal stromal cells; Patch clamp.