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Article: The membrane permeable calcium chelator BAPTA-AM directly blocks human ether a-go-go-related gene potassium channels stably expressed in HEK 293 cells

TitleThe membrane permeable calcium chelator BAPTA-AM directly blocks human ether a-go-go-related gene potassium channels stably expressed in HEK 293 cells
Authors
Issue Date2007
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharm
Citation
Biochemical Pharmacology, 2007, v. 74 n. 11, p. 1596-1607 How to Cite?
AbstractBAPTA-AM is a well-known membrane permeable Ca 2+ chelator. The present study found that BAPTA-AM rapidly and reversibly suppressed human ether a-go-go-related gene (hERG or Kv11.1) K + current, human Kv1.3 and human Kv1.5 channel currents stably expressed in HEK 293 cells, and the effects were not related to Ca 2+ chelation. The externally applied BAPTA-AM inhibited hERG channels in a concentration-dependent manner (IC 50: 1.3 μM). Blockade of hERG channels was dependent on channel opening, and tonic block was minimal. Steady-state activation V 0.5 of hERG channels was negatively shifted by 8.5 mV (from -3.7 ± 2.8 of control to -12.2 ± 3.1 mV, P < 0.01), while inactivation V 0.5 was negatively shifted by 6.1 mV (from -37.9 ± 2.0 mV of control to -44.0 ± 1.6 mV, P < 0.05) with application of 3 μM BAPTA-AM. The S6 mutant Y652A and the pore helix mutant S631A significantly attenuated blockade by BAPTA-AM at 10 μM causing profound blockade of wild-type hERG channels. In addition, BAPTA-AM inhibited hKv1.3 and hKv1.5 channels in a concentration-dependent manner (IC 50: 1.45 and 1.23 μM, respectively), and the blockade of these two types of channels was also dependent on channel opening. Moreover, EGTA-AM was found to be an open channel blocker of hERG, hKv1.3, hKv1.5 channels, though its efficacy is weaker than that of BAPTA-AM. These results indicate that the membrane permeable Ca 2+ chelator BAPTA-AM (also EGTA-AM) exerts an open channel blocking effect on hERG, hKv1.3 and hKv1.5 channels. © 2007 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/76251
ISSN
2015 Impact Factor: 5.091
2015 SCImago Journal Rankings: 2.263
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTang, Qen_HK
dc.contributor.authorJin, MWen_HK
dc.contributor.authorXiang, JZen_HK
dc.contributor.authorDong, MQen_HK
dc.contributor.authorSun, HYen_HK
dc.contributor.authorLau, CPen_HK
dc.contributor.authorLi, GRen_HK
dc.date.accessioned2010-09-06T07:19:14Z-
dc.date.available2010-09-06T07:19:14Z-
dc.date.issued2007en_HK
dc.identifier.citationBiochemical Pharmacology, 2007, v. 74 n. 11, p. 1596-1607en_HK
dc.identifier.issn0006-2952en_HK
dc.identifier.urihttp://hdl.handle.net/10722/76251-
dc.description.abstractBAPTA-AM is a well-known membrane permeable Ca 2+ chelator. The present study found that BAPTA-AM rapidly and reversibly suppressed human ether a-go-go-related gene (hERG or Kv11.1) K + current, human Kv1.3 and human Kv1.5 channel currents stably expressed in HEK 293 cells, and the effects were not related to Ca 2+ chelation. The externally applied BAPTA-AM inhibited hERG channels in a concentration-dependent manner (IC 50: 1.3 μM). Blockade of hERG channels was dependent on channel opening, and tonic block was minimal. Steady-state activation V 0.5 of hERG channels was negatively shifted by 8.5 mV (from -3.7 ± 2.8 of control to -12.2 ± 3.1 mV, P < 0.01), while inactivation V 0.5 was negatively shifted by 6.1 mV (from -37.9 ± 2.0 mV of control to -44.0 ± 1.6 mV, P < 0.05) with application of 3 μM BAPTA-AM. The S6 mutant Y652A and the pore helix mutant S631A significantly attenuated blockade by BAPTA-AM at 10 μM causing profound blockade of wild-type hERG channels. In addition, BAPTA-AM inhibited hKv1.3 and hKv1.5 channels in a concentration-dependent manner (IC 50: 1.45 and 1.23 μM, respectively), and the blockade of these two types of channels was also dependent on channel opening. Moreover, EGTA-AM was found to be an open channel blocker of hERG, hKv1.3, hKv1.5 channels, though its efficacy is weaker than that of BAPTA-AM. These results indicate that the membrane permeable Ca 2+ chelator BAPTA-AM (also EGTA-AM) exerts an open channel blocking effect on hERG, hKv1.3 and hKv1.5 channels. © 2007 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharmen_HK
dc.relation.ispartofBiochemical Pharmacologyen_HK
dc.rightsBiochemical Pharmacology. Copyright © Elsevier Inc.en_HK
dc.subject.meshCalcium - metabolismen_HK
dc.subject.meshCell Lineen_HK
dc.subject.meshCell Membrane Permeability - drug effectsen_HK
dc.subject.meshChelating Agents - pharmacologyen_HK
dc.subject.meshDose-Response Relationship, Drugen_HK
dc.subject.meshEgtazic Acid - analogs & derivatives - pharmacologyen_HK
dc.subject.meshEther-A-Go-Go Potassium Channels - genetics - physiologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshKv1.3 Potassium Channel - genetics - physiologyen_HK
dc.subject.meshKv1.5 Potassium Channel - genetics - physiologyen_HK
dc.subject.meshMembrane Potentials - drug effectsen_HK
dc.subject.meshMutagenesis, Site-Directeden_HK
dc.subject.meshPorins - genetics - physiologyen_HK
dc.subject.meshTransfectionen_HK
dc.titleThe membrane permeable calcium chelator BAPTA-AM directly blocks human ether a-go-go-related gene potassium channels stably expressed in HEK 293 cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0006-2952&volume=74&issue=11&spage=1596&epage=607&date=2007&atitle=The+membrane+permeable+calcium+chelator+BAPTA-AM+directly+blocks+human+ether+a-go-go-related+gene+potassium+channels+stably+expressed+in+HEK+293+cells.++++en_HK
dc.identifier.emailLi, GR:grli@hkucc.hku.hken_HK
dc.identifier.authorityLi, GR=rp00476en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.bcp.2007.07.042en_HK
dc.identifier.pmid17826747-
dc.identifier.scopuseid_2-s2.0-35348955352en_HK
dc.identifier.hkuros139381en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-35348955352&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume74en_HK
dc.identifier.issue11en_HK
dc.identifier.spage1596en_HK
dc.identifier.epage1607en_HK
dc.identifier.isiWOS:000251118600005-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridTang, Q=40861778800en_HK
dc.identifier.scopusauthoridJin, MW=35932258500en_HK
dc.identifier.scopusauthoridXiang, JZ=10641709700en_HK
dc.identifier.scopusauthoridDong, MQ=35081870400en_HK
dc.identifier.scopusauthoridSun, HY=35723049200en_HK
dc.identifier.scopusauthoridLau, CP=7401968501en_HK
dc.identifier.scopusauthoridLi, GR=7408462932en_HK

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