4.3 Article

Potassium channel currents in rat mesenchymal stem cells and their possible roles in cell proliferation

Journal

Publisher

WILEY
DOI: 10.1111/j.1440-1681.2008.04964.x

Keywords

amiodarone; K+ channels; proliferation; stem cells

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1. Mesenchymal stem cells (MSC) have shown considerable promise for the regeneration and repair of damaged tissue. However, the electrophysiological properties of K+ channels in MSC are not well established and little is known about the role of K+ channels in the regulation of MSC proliferation. 2. We detected three distinct outward currents in MSC: (i) a delayed rectifier current (IKDR); (ii) a Ca2+-activated K+ current (IKCa); and (iii) a transient outward K+ current (Ito). All three were present either alone or in combination in almost all cells (90%) investigated. However, 10% of cells did not express a functional current within physiological potentials. 3. Reverse transcription-polymerase chain reaction was used to identify mRNA associated with functional ionic currents. Kv1.2 and Kv2.1 were associated with IKDR; Slo and KCNN4 were associated with IKCa; and Kv1.4 and Kv4.3 were associated with Ito. 4. The Kv channel blockers amiodarone, tetraethylammonium and verapamil, as well as increased extracellular K+ levels, inhibited proliferation of cultured MSC. 5. In MSC treated with Kv channel blockers or an increased extracellular concentration of K+, the proportion of cells in the S phase decreased significantly and the proportion of cells in the G(0)/G(1) phase tended to increase, indicating that the cells were prevented from entering the S phase of the cell cycle. 6. Our findings suggest that rat MSC heterogeneously express distinct types of K+ current, of which the voltage-gated IKDR-like K+ current is most common. Kv channel activity modulates the progression of the cell cycle, affecting the proliferation of MSC.

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