Potassium channel currents in rat mesenchymal stem cells and their possible roles in cell proliferation.
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. We detected three distinct outward currents in MSC: (i) a delayed rectifier current (IK(DR)); (ii) a Ca2+-activated K+ current (IK(Ca)); 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. Reverse transcription-polymerase chain reaction was used to identify mRNA associated with functional ionic currents. Kv1.2 and Kv2.1 were associated with IK(DR); Slo and KCNN4 were associated with IK(Ca); and Kv1.4 and Kv4.3 were associated with Ito. The Kv channel blockers amiodarone, tetraethylammonium and verapamil, as well as increased extracellular K+ levels, inhibited proliferation of cultured MSC. 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. Our findings suggest that rat MSC heterogeneously express distinct types of K+ current, of which the voltage-gated IK(DR)-like K+ current is most common. Kv channel activity modulates the progression of the cell cycle, affecting the proliferation of MSC.
Wang
Shao-Ping
SP
Division of Cardiology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Wang
Jian-An
JA
Luo
Rong-Hua
RH
Cui
Wen-Yu
WY
Wang
Hai
H
D000638:Amiodarone / Q000494:pharmacology; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D021122:Protein Subunits; D012333:RNA, Messenger; D014700:Verapamil; D009543:Nifedipine; D000638:Amiodarone