Linked Life Data

15371638

Source:http://linkedlifedata.com/resource/pubmed/id/15371638

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-9-16
pubmed:abstractText
The kinetics of voltage-dependent inactivation of the rapidly activating delayed rectifier, IKr, are unique among K+ channels. The human ether-a-gogo-related gene (HERG) encodes the pore-forming subunit of IKr and shares a high degree of homology with ether-a-gogo (EAG) channels that do not inactivate. Within those segments thought to contribute to the channel pore, HERG possesses several serine residues that are not present in EAG channels. Two of these serines, S620 and S631, are known to be required for inactivation. We now show that a third serine, S641, which resides in the outer portion of the sixth transmembrane segment, is also critical for normal inactivation. As with the other serines, S641 is also involved in maintaining ion selectivity of the HERG channel and alters sensitivity to block by E4031. Larger charged or polar substitutions (S641D and S641T) disrupted C-type inactivation in HERG. Smaller aliphatic and more conservative substitutions (S641A and S641C) facilitated C-type inactivation. Our data show that, like S620 and S631, S641 is another key residue for the rapid inactivation. The altered inactivation of mutations at S620, S631, and S641 were dominant, suggesting that a network of hydroxyl side chains is required for the unique inactivation, permeation, and rectification of HERG channels.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1559-0283
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25-40
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
S641 contributes HERG K+ channel inactivation.
pubmed:affiliation
Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural