Electrophysiological properties of human induced pluripotent stem cells

Peng Jiang, Stephanie N. Rushing, Chi Wing Kong, Jidong Fu, Deborah Kuo Ti Lieu, Camie W. Chan, Wenbin Deng, Ronald A. Li

Research output: Contribution to journalArticle

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Abstract

Human embryonic stem cells (hESCs) can self-renew while maintaining their pluripotency. Direct reprogramming of adult somatic cells to induced pluripotent stem cells (iPSCs) has been reported. Although hESCs and human iPSCs have been shown to share a number of similarities, such basic properties as the electrophysiology of iPSCs have not been explored. Previously, we reported that several specialized ion channels are functionally expressed in hESCs. Using transcriptomic analyses as a guide, we observed tetraethylammonium (TEA)-sensitive (IC50 = 3.3 ± 2.7 mM) delayed rectifier K + currents (IKDR) in 105 of 110 single iPSCs (15.4 ± 0.9 pF). IKDR in iPSCs displayed a current density of 7.6 ± 3.8 pA/pF at +40 mV. The voltage for 50% activation (V1/2) was -7.9 ± 2.0 mV, slope factor k = 9.1 ± 1.5. However, Ca 2+-activated K+ current (IKCa), hyperpolarization-activated pacemaker current (If), and voltage-gated sodium channel (NaV) and voltage-gated calcium channel (Ca V) currents could not be measured. TEA inhibited iPSC proliferation (EC50 = 7.8 ± 1.2 mM) and viability (EC50 = 5.5 ± 1.0 mM). By contrast, 4-aminopyridine (4-AP) inhibited viability (EC50 = 4.5 ± 0.5 mM) but had less effect on proliferation (EC50 = 0.9 ± 0.5 mM). Cell cycle analysis further revealed that K+ channel blockers inhibited proliferation primarily by arresting the mitotic phase. TEA and 4-AP had no effect on iPSC differentiation as gauged by ability to form embryoid bodies and expression of germ layer markers after induction of differentiation. Neither iberiotoxin nor apamin had any function effects, consistent with the lack of IKCa in iPSCs. Our results reveal further differences and similarities between human iPSCs and hESCs. A better understanding of the basic biology of iPSCs may facilitate their ultimate clinical application.

Original languageEnglish (US)
Pages (from-to)C486-C495
JournalAmerican Journal of Physiology - Cell Physiology
Volume298
Issue number3
DOIs
StatePublished - Mar 1 2010

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Induced Pluripotent Stem Cells
Tetraethylammonium
4-Aminopyridine
Voltage-Gated Sodium Channels
Embryoid Bodies
Apamin
Germ Layers
Electrophysiology
Calcium Channels
Ion Channels
Inhibitory Concentration 50
Cell Differentiation
Cell Cycle
Cell Proliferation

Keywords

  • Ion channels
  • Patch-clamp recording
  • Potassium currents

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Jiang, P., Rushing, S. N., Kong, C. W., Fu, J., Lieu, D. K. T., Chan, C. W., ... Li, R. A. (2010). Electrophysiological properties of human induced pluripotent stem cells. American Journal of Physiology - Cell Physiology, 298(3), C486-C495. https://doi.org/10.1152/ajpcell.00251.2009

Electrophysiological properties of human induced pluripotent stem cells. / Jiang, Peng; Rushing, Stephanie N.; Kong, Chi Wing; Fu, Jidong; Lieu, Deborah Kuo Ti; Chan, Camie W.; Deng, Wenbin; Li, Ronald A.

In: American Journal of Physiology - Cell Physiology, Vol. 298, No. 3, 01.03.2010, p. C486-C495.

Research output: Contribution to journalArticle

Jiang, P, Rushing, SN, Kong, CW, Fu, J, Lieu, DKT, Chan, CW, Deng, W & Li, RA 2010, 'Electrophysiological properties of human induced pluripotent stem cells', American Journal of Physiology - Cell Physiology, vol. 298, no. 3, pp. C486-C495. https://doi.org/10.1152/ajpcell.00251.2009
Jiang, Peng ; Rushing, Stephanie N. ; Kong, Chi Wing ; Fu, Jidong ; Lieu, Deborah Kuo Ti ; Chan, Camie W. ; Deng, Wenbin ; Li, Ronald A. / Electrophysiological properties of human induced pluripotent stem cells. In: American Journal of Physiology - Cell Physiology. 2010 ; Vol. 298, No. 3. pp. C486-C495.
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