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Article: Electrophysiological properties of human induced pluripotent stem cells

TitleElectrophysiological properties of human induced pluripotent stem cells
Authors
KeywordsIon channels
Patch-clamp recording
Potassium currents
Issue Date2010
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpcell.physiology.org/
Citation
American Journal Of Physiology - Cell Physiology, 2010, v. 298 n. 3, p. C486-C495 How to Cite?
AbstractHuman 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 (IC 50 = 3.3 ± 2.7 mM) delayed rectifier K + currents (I KDR) in 105 of 110 single iPSCs (15.4 ± 0.9 pF). I KDR in iPSCs displayed a current density of 7.6 ± 3.8 pA/pF at +40 mV. The voltage for 50% activation (V 1/2) was -7.9 ± 2.0 mV, slope factor k = 9.1 ± 1.5. However, Ca 2+-activated K + current (I KCa), hyperpolarization-activated pacemaker current (I f), and voltage-gated sodium channel (Na V) and voltage-gated calcium channel (Ca V) currents could not be measured. TEA inhibited iPSC proliferation (EC 50 = 7.8 ± 1.2 mM) and viability (EC 50 = 5.5 ± 1.0 mM). By contrast, 4-aminopyridine (4-AP) inhibited viability (EC 50 = 4.5 ± 0.5 mM) but had less effect on proliferation (EC 50 = 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 I KCa 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. Copyright © 2010 the American Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/143127
ISSN
2015 Impact Factor: 3.395
2015 SCImago Journal Rankings: 1.893
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of HealthR01-NS-059043
R01-ES-015988
R01-HL-72857
California Institute for Regenerative Medicine
National Multiple Sclerosis Society
Shriners Hospitals for Children
CC Wong Foundation Stem Cell Fund
Funding Information:

This work was in part supported by grants from the National Institutes of Health (R01-NS-059043, R01-ES-015988 to W. Deng and R01-HL-72857 to R. A. Li), the California Institute for Regenerative Medicine (to R. A. Li), the National Multiple Sclerosis Society (to W. Deng), Shriners Hospitals for Children (to W. Deng), and the CC Wong Foundation Stem Cell Fund (to R. A. Li).

References

 

DC FieldValueLanguage
dc.contributor.authorJiang, Pen_HK
dc.contributor.authorRushing, SNen_HK
dc.contributor.authorKong, CWen_HK
dc.contributor.authorFu, Jen_HK
dc.contributor.authorLieu, DKTen_HK
dc.contributor.authorChan, CWen_HK
dc.contributor.authorDeng, Wen_HK
dc.contributor.authorLi, RAen_HK
dc.date.accessioned2011-11-02T03:05:28Z-
dc.date.available2011-11-02T03:05:28Z-
dc.date.issued2010en_HK
dc.identifier.citationAmerican Journal Of Physiology - Cell Physiology, 2010, v. 298 n. 3, p. C486-C495en_HK
dc.identifier.issn0363-6143en_HK
dc.identifier.urihttp://hdl.handle.net/10722/143127-
dc.description.abstractHuman 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 (IC 50 = 3.3 ± 2.7 mM) delayed rectifier K + currents (I KDR) in 105 of 110 single iPSCs (15.4 ± 0.9 pF). I KDR in iPSCs displayed a current density of 7.6 ± 3.8 pA/pF at +40 mV. The voltage for 50% activation (V 1/2) was -7.9 ± 2.0 mV, slope factor k = 9.1 ± 1.5. However, Ca 2+-activated K + current (I KCa), hyperpolarization-activated pacemaker current (I f), and voltage-gated sodium channel (Na V) and voltage-gated calcium channel (Ca V) currents could not be measured. TEA inhibited iPSC proliferation (EC 50 = 7.8 ± 1.2 mM) and viability (EC 50 = 5.5 ± 1.0 mM). By contrast, 4-aminopyridine (4-AP) inhibited viability (EC 50 = 4.5 ± 0.5 mM) but had less effect on proliferation (EC 50 = 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 I KCa 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. Copyright © 2010 the American Physiological Society.en_HK
dc.languageengen_US
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpcell.physiology.org/en_HK
dc.relation.ispartofAmerican Journal of Physiology - Cell Physiologyen_HK
dc.rightsAmerican Journal of Physiology: Cell Physiology. Copyright © American Physiological Society.-
dc.rightsThis is an unofficial adaptation or translation of an article that appeared in a publication of the American Physiological Society. The American Physiological Society has not endorsed the content of this adaptation or translation, or the context of its use.-
dc.subjectIon channelsen_HK
dc.subjectPatch-clamp recordingen_HK
dc.subjectPotassium currentsen_HK
dc.subject.meshCalcium Channels - metabolismen_US
dc.subject.meshDelayed Rectifier Potassium Channels - antagonists and inhibitors - genetics - metabolismen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshInduced Pluripotent Stem Cells - drug effects - metabolismen_US
dc.subject.meshPotassium - metabolismen_US
dc.titleElectrophysiological properties of human induced pluripotent stem cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0363-6143&volume=298&issue=3&spage=C486&epage=C495 &date=2010&atitle=Electrophysiological+properties+of+human+induced+pluripotent+stem+cells-
dc.identifier.emailKong, CW:marcokong@hku.hken_HK
dc.identifier.emailChan, CW:camchan@hku.hken_HK
dc.identifier.emailLi, RA:ronaldli@hkucc.hku.hken_HK
dc.identifier.authorityKong, CW=rp01563en_HK
dc.identifier.authorityChan, CW=rp01311en_HK
dc.identifier.authorityLi, RA=rp01352en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1152/ajpcell.00251.2009en_HK
dc.identifier.pmid19955484-
dc.identifier.pmcidPMC2838581-
dc.identifier.scopuseid_2-s2.0-77749264613en_HK
dc.identifier.hkuros175072-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77749264613&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume298en_HK
dc.identifier.issue3en_HK
dc.identifier.spageC486en_HK
dc.identifier.epageC495en_HK
dc.identifier.isiWOS:000274931700010-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridJiang, P=36022461000en_HK
dc.identifier.scopusauthoridRushing, SN=25121769500en_HK
dc.identifier.scopusauthoridKong, CW=36784634200en_HK
dc.identifier.scopusauthoridFu, J=7401722481en_HK
dc.identifier.scopusauthoridLieu, DKT=7003924538en_HK
dc.identifier.scopusauthoridChan, CW=12240386600en_HK
dc.identifier.scopusauthoridDeng, W=7202223503en_HK
dc.identifier.scopusauthoridLi, RA=7404724466en_HK

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