Calcium-gated K+ channels of the KCa1.1- and KCa3.1-type couple intracellular Ca2+ signals to membrane hyperpolarization in mesenchymal stromal cells from the human adipose tissue

• Published in: Pflügers Archiv Vol. 469; no. 2; pp. 349 - 362
• Main Authors: Tarasov, Michail V., Bystrova, Marina F., Kotova, Polina D., Rogachevskaja, Olga A., Sysoeva, Veronika Y., Kolesnikov, Stanislav S.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2017
• Subjects: Biomedical and Life Sciences; Biomedicine; Cell Biology; Human Physiology; Molecular Medicine; Neurosciences; Receptors; Signaling and Cell Physiology; Adenosine; channels; Mesenchymal stromal cells; Patch clamp; imaging; ATP; Ca; activated K
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-016-1932-4

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 2+ in the MSC cytoplasm. A variety of Ca 2+ -gated ion channels may couple Ca 2+ 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 2+ transients or exhibiting spontaneous Ca 2+ oscillations, Ca 2+ bursts were associated with hyperpolarization mediated by Ca 2+ -gated K + channels. The expression analysis revealed transcripts for KCNMA1 and KCNN4 genes encoding for Ca 2+ -activated K + channels of large (K Ca 1.1) and intermediate (K Ca 3.1) conductance, respectively. Moreover, transcripts for the Ca 2+ -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 2+ stimulated K + currents that were inhibited with iberiotoxin. This suggested that K Ca 1.1 channels are invariably expressed in MSCs. In ATP- and adenosine-responsive cells, iberiotoxin and TRAM-34 diminished electrical responses, implicating both K Ca 1.1 and K Ca 3.1 channels in coupling agonist-dependent Ca 2+ signals to membrane voltage. Functional tests pointed at the existence of two separate MSC subpopulations exhibiting Ca 2+ -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, K Ca 1.1 channels are likely to represent the dominant type of Ca 2+ -activated K + channels in MSCs, which can serve in concert with K Ca 3.1 channels as effectors downstream of G-protein-coupled receptor (GPCR)-mediated Ca 2+ signaling.