Document Detail

Different relevance of inactivation and F468 residue in the mechanisms of hEag1 channel blockage by astemizole, imipramine and dofetilide.
MedLine Citation:
PMID:  16949586     Owner:  NLM     Status:  MEDLINE    
The relevance of a point mutation at the C-terminal end of the S6 helix (F468) and the introduction of C-type inactivation in the blockage of hEag1 channels by astemizole, imipramine and dofetilide was tested. C-type inactivation decreased block by astemizole and dofetilide but not imipramine, suggesting different binding sites in the channel. F468C mutation increased IC(50) for astemizole and imipramine but in contrast to HERG channels, only slightly for dofetilide. Together with measurements on recovery of blocking, our observations indicate that the mechanism of hEag1 blockage by each of these drugs is different, and suggest relevant structural differences between hEag1 and HERG channels.
David Gómez-Varela; Constanza Contreras-Jurado; Simone Furini; Rafael García-Ferreiro; Walter Stühmer; Luis A Pardo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-08-28
Journal Detail:
Title:  FEBS letters     Volume:  580     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-12     Completed Date:  2006-10-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  5059-66     Citation Subset:  IM    
Max-Planck-Institute of Experimental Medicine, Department of Molecular Biology of Neuronal Signals, Hermann-Rein-Str. 3, 37075 Göttingen, Germany.
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MeSH Terms
Astemizole / chemistry,  pharmacology*
Benzopyrans / pharmacology
Ether-A-Go-Go Potassium Channels / metabolism*
Imipramine / pharmacology*
Ion Channel Gating / drug effects*
Models, Molecular
Phenethylamines / pharmacology*
Piperidines / pharmacology
Point Mutation / genetics*
Potassium Channel Blockers / pharmacology*
Structure-Activity Relationship
Sulfonamides / pharmacology*
Reg. No./Substance:
0/Benzopyrans; 0/Ether-A-Go-Go Potassium Channels; 0/KCNH1 protein, human; 0/Phenethylamines; 0/Piperidines; 0/Potassium Channel Blockers; 0/Sulfonamides; 115256-11-6/dofetilide; 150481-98-4/L 706000; 50-49-7/Imipramine; 68844-77-9/Astemizole

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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