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Article: The calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide directly blocks human ether à-go-go-related gene potassium channels stably expressed in human embryonic kidney 293 cells

TitleThe calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide directly blocks human ether à-go-go-related gene potassium channels stably expressed in human embryonic kidney 293 cells
Authors
KeywordshERG channel
hK IR2.1
hK v1.5
W-7
Issue Date2010
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
Citation
British Journal Of Pharmacology, 2010, v. 161 n. 4, p. 872-884 How to Cite?
AbstractBACKGROUND AND PURPOSE N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide (W-7) is a well-known calmodulin inhibitor used to study calmodulin regulation of intracellular Ca 2+ signalling-related process. Here, we have determined whether W-7 would inhibit human ether gene (hERG or K v11.1) potassium channels, hK v1.5 channels or hK IR2.1 channels expressed in human embryonic kidney (HEK) 293 cells. EXPERIMENTAL APPROACH The hERG channel current, hK v1.5 channel current or hK IR2.1 channel current was recorded with a whole-cell patch clamp technique. KEY RESULTS It was found that the calmodulin inhibitor W-7 blocked hERG, hK v1.5 and hK IR2.1 channels. W-7 decreased the hERG current (I hERG) in a concentration-dependent manner (IC 50: 3.5 μM), and the inhibition was more significant at depolarization potentials between +10 and +60 mV. The hERG mutations in the S6 region Y652A and F656V, and in the pore helix S631A, had the IC 50s of 5.5, 9.8 and 25.4 μM respectively. In addition, the compound inhibited hK v1.5 and hK IR2.1 channels with IC 50s of 6.5 and 13.4 μM respectively. CONCLUSION AND IMPLICATIONS These results indicate that the calmodulin inhibitor W-7 exerts a direct channel-blocking effect on hERG, hK v1.5 and hK IR2.1 channels stably expressed in HEK 293 cells. Caution should be taken in the interpretation of calmodulin regulation of ion channels with W-7. © 2010 The British Pharmacological Society.
Persistent Identifierhttp://hdl.handle.net/10722/141988
ISSN
2015 Impact Factor: 5.259
2015 SCImago Journal Rankings: 2.368
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Sun Chieh Yeh Heart Foundation of Hong Kong
Canadian Institutes of Health ResearchMOP 84229
Funding Information:

The study was supported in part by Sun Chieh Yeh Heart Foundation of Hong Kong to G-R.L. S.Z. is supported by the Canadian Institutes of Health Research (MOP 84229). The authors thank Dr G. Robertson (University of Wisconsin, Madison, WI, USA) for providing the vector of hERG/pcDNA3; Dr M. Tamkun (Colorado State University, CO, USA) for providing the vector of hK<INF>v</INF>1.5/pBKCMV; and Dr Carol A. Vandenberg, University of California at Santa Barbara, CA, USA) for providing the vector of hK<INF>IR</INF>2.1 channels.

References

 

DC FieldValueLanguage
dc.contributor.authorZhang, XHen_HK
dc.contributor.authorJin, MWen_HK
dc.contributor.authorSun, HYen_HK
dc.contributor.authorZhang, Sen_HK
dc.contributor.authorLi, GRen_HK
dc.date.accessioned2011-10-04T06:34:52Z-
dc.date.available2011-10-04T06:34:52Z-
dc.date.issued2010en_HK
dc.identifier.citationBritish Journal Of Pharmacology, 2010, v. 161 n. 4, p. 872-884en_HK
dc.identifier.issn0007-1188en_HK
dc.identifier.urihttp://hdl.handle.net/10722/141988-
dc.description.abstractBACKGROUND AND PURPOSE N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide (W-7) is a well-known calmodulin inhibitor used to study calmodulin regulation of intracellular Ca 2+ signalling-related process. Here, we have determined whether W-7 would inhibit human ether gene (hERG or K v11.1) potassium channels, hK v1.5 channels or hK IR2.1 channels expressed in human embryonic kidney (HEK) 293 cells. EXPERIMENTAL APPROACH The hERG channel current, hK v1.5 channel current or hK IR2.1 channel current was recorded with a whole-cell patch clamp technique. KEY RESULTS It was found that the calmodulin inhibitor W-7 blocked hERG, hK v1.5 and hK IR2.1 channels. W-7 decreased the hERG current (I hERG) in a concentration-dependent manner (IC 50: 3.5 μM), and the inhibition was more significant at depolarization potentials between +10 and +60 mV. The hERG mutations in the S6 region Y652A and F656V, and in the pore helix S631A, had the IC 50s of 5.5, 9.8 and 25.4 μM respectively. In addition, the compound inhibited hK v1.5 and hK IR2.1 channels with IC 50s of 6.5 and 13.4 μM respectively. CONCLUSION AND IMPLICATIONS These results indicate that the calmodulin inhibitor W-7 exerts a direct channel-blocking effect on hERG, hK v1.5 and hK IR2.1 channels stably expressed in HEK 293 cells. Caution should be taken in the interpretation of calmodulin regulation of ion channels with W-7. © 2010 The British Pharmacological Society.en_HK
dc.languageeng-
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1en_HK
dc.relation.ispartofBritish Journal of Pharmacologyen_HK
dc.rightsBritish Journal of Pharmacology. Copyright © John Wiley & Sons Ltd.-
dc.subjecthERG channelen_HK
dc.subjecthK IR2.1en_HK
dc.subjecthK v1.5en_HK
dc.subjectW-7en_HK
dc.subject.meshEther-A-Go-Go Potassium Channels - antagonists and inhibitors - genetics-
dc.subject.meshKidney - cytology-
dc.subject.meshKv1.5 Potassium Channel - antagonists and inhibitors-
dc.subject.meshPotassium Channels, Inwardly Rectifying - antagonists and inhibitors-
dc.subject.meshSulfonamides - administration and dosage - pharmacology-
dc.titleThe calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide directly blocks human ether à-go-go-related gene potassium channels stably expressed in human embryonic kidney 293 cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0007-1188&volume=161&issue=4&spage=872&epage=884&date=2010&atitle=The+calmodulin+inhibitor+N-(6-aminohexyl)-5-chloro-1-naphthalene+sulphonamide+directly+blocks+human+ether+à-go-go-related+gene+potassium+channels+stably+expressed+in+human+embryonic+kidney+293+cells-
dc.identifier.emailLi, GR:grli@hkucc.hku.hken_HK
dc.identifier.authorityLi, GR=rp00476en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1111/j.1476-5381.2010.00916.xen_HK
dc.identifier.pmid20860665-
dc.identifier.pmcidPMC2992901-
dc.identifier.scopuseid_2-s2.0-77957222441en_HK
dc.identifier.hkuros183234-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77957222441&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume161en_HK
dc.identifier.issue4en_HK
dc.identifier.spage872en_HK
dc.identifier.epage884en_HK
dc.identifier.isiWOS:000282179000012-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridZhang, XH=7410270356en_HK
dc.identifier.scopusauthoridJin, MW=35932258500en_HK
dc.identifier.scopusauthoridSun, HY=35723049200en_HK
dc.identifier.scopusauthoridZhang, S=8655018900en_HK
dc.identifier.scopusauthoridLi, GR=7408462932en_HK

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