Linked Life Data

11134230

Source:http://linkedlifedata.com/resource/pubmed/id/11134230

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-1-29
pubmed:abstractText
I(Ks), a slowly activating delayed rectifier K(+) current through channels formed by the assembly of two subunits KCNQ1 (KvLQT1) and KCNE1 (minK), contributes to the control of the cardiac action potential duration. Coassembly of the two subunits is essential in producing the characteristic and physiologically critical kinetics of assembled channels, but it is not yet clear where or how these subunits interact. Previous investigations of external access to the KCNE1 protein in assembled I(Ks) channels relied on occlusion of the pore by extracellular application of TEA(+), despite the very low TEA(+) sensitivity (estimated EC(50) > 100 mM) of channels encoded by coassembly of wild-type KCNQ1 with the wild type (WT) or a series of cysteine-mutated KCNE1 constructs. We have engineered a high affinity TEA(+) binding site into the h-KCNQ1 channel by either a single (V319Y) or double (K318I, V319Y) mutation, and retested it for pore-delimited access to specific sites on coassembled KCNE1 subunits. Coexpression of either KCNQ1 construct with WT KCNE1 in Chinese hamster ovary cells does not alter the TEA(+) sensitivity of the homomeric channels (IC(50) approximately 0.4 mM [TEA(+)](out)), providing evidence that KCNE1 coassembly does not markedly alter the structure of the outer pore of the KCNQ1 channel. Coexpression of a cysteine-substituted KCNE1 (F54C) with V319Y significantly increases the sensitivity of channels to external Cd(2+), but neither the extent of nor the kinetics of the onset of (or the recovery from) Cd(2+) block was affected by [TEA(+)](o) at 10x the IC(50) for channel block. These data strongly suggest that access of Cd(2+) to the cysteine-mutated site on KCNE1 is independent of pore occlusion caused by TEA(+) binding to the outer region of the KCNE1/V319Y pore, and that KCNE1 does not reside within the pore region of the assembled channels.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-10207306, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-10219239, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-10352341, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-10646604, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-10709243, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-10794658, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-10838601, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-10868746, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-10884227, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-1384130, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-1550673, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-2000494, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-2218530, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-3194754, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-7568104, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-7748553, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-8081712, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-8204619, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-8270910, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-8562074, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-8785054, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-8881507, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-8900282, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-8900283, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-9152391, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-9201970, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-9230439, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-9354802, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-9468141, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-9525859, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-9625865, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-9711606, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-9834138, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-9834139, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-9836639, http://linkedlifedata.com/resource/pubmed/commentcorrection/11134230-9852064
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-1295
pubmed:author
pubmed:issnType
Print
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
43-52
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
TEA(+)-sensitive KCNQ1 constructs reveal pore-independent access to KCNE1 in assembled I(Ks) channels.
pubmed:affiliation
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't