title: Potassium channel currents in rat mesenchymal stem cells and their possible roles in cell proliferation.
abstract: 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.
authors.affiliation: Division of Cardiology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Shao-Ping
authors.initials: SP
authors.lastname: Wang
authors.forename: Jian-An
authors.initials: JA
authors.lastname: Wang
authors.forename: Rong-Hua
authors.initials: RH
authors.lastname: Luo
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Cui
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
mesh_terms: 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
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D021122:Protein Subunits; D012333:RNA, Messenger; D014700:Verapamil; D009543:Nifedipine; D000638:Amiodarone