Calcium-gated K channels of the K1.1- and K3.1-type couple intracellular Ca signals to membrane hyperpolarization in mesenchymal stromal cells from the human adipose tissue.

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 Ca in the MSC cytoplasm. A variety of Ca-gated ion channels may couple Ca 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 Ca transients or exhibiting spontaneous Ca oscillations, Ca bursts were associated with hyperpolarization mediated by Ca-gated K channels. The expression analysis revealed transcripts for KCNMA1 and KCNN4 genes encoding for Ca-activated K channels of large (K1.1) and intermediate (K3.1) conductance, respectively. Moreover, transcripts for the Ca-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 Ca stimulated K currents that were inhibited with iberiotoxin. This suggested that K1.1 channels are invariably expressed in MSCs. In ATP- and adenosine-responsive cells, iberiotoxin and TRAM-34 diminished electrical responses, implicating both K1.1 and K3.1 channels in coupling agonist-dependent Ca signals to membrane voltage. Functional tests pointed at the existence of two separate MSC subpopulations exhibiting Ca-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, K1.1 channels are likely to represent the dominant type of Ca-activated K channels in MSCs, which can serve in concert with K3.1 channels as effectors downstream of G-protein-coupled receptor (GPCR)-mediated Ca signaling.