Linked Life Data

10825393

Source:http://linkedlifedata.com/resource/pubmed/id/10825393

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-6-22
pubmed:abstractText
Channels formed by coassembly of the KCNQ1 (KvLQT1) subunit and the minK subunit underlie slowly activating cardiac delayed rectifier (I(Ks)) in the heart, whereas two other members of the KCNQ channel family, KCNQ2 and KCNQ3, coassemble to underlie the M current in the nervous system. Because of their important physiological function, KCNQ channels have potential as drug targets, and an understanding of possible mechanisms that would enable tissue-specific targeting of these channels will be of significant value to drug development. In this study, we examined the role of the minK subunit in determining the response of KCNQ1 channels to blockade by the cognitive enhancer XE991. Coexpression with minK markedly decreased the sensitivity of KCNQ1 to blockade by XE991. When measured at the end of a 500-ms step, XE991 blockade of the KCNQ1+minK current had a K(D) value of 11.1 +/- 1.8 microM, approximately 14-fold less sensitive than the block of the KCNQ1 current (K(D) = 0.78 +/- 0.05 microM). In addition, XE991 reduced activation and deactivation time constants and caused a rightward shift in the activation curve of KCNQ1+minK, but affected none of these parameters for KCNQ1 alone. Also, XE991 block of KCNQ1+minK, but not of KCNQ1, was time- and voltage-dependent. We conclude that the presence of minK in the I(Ks) channel complex gives rise to differential sensitivity of KCNQ and I(Ks) channels to blockade by XE991. Our results have implications for drug development by demonstrating the important potential role of accessory subunits in determining the pharmacological properties of KCNQ channels.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/10,10-bis(4-pyridinylmethyl)-9(10H)-..., http://linkedlifedata.com/resource/pubmed/chemical/Anthracenes, http://linkedlifedata.com/resource/pubmed/chemical/KCNQ2 Potassium Channel, http://linkedlifedata.com/resource/pubmed/chemical/KCNQ2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/KCNQ3 Potassium Channel, http://linkedlifedata.com/resource/pubmed/chemical/KCNQ3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Nootropic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels, http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels, Voltage-Gated, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins, http://linkedlifedata.com/resource/pubmed/chemical/potassium channel protein I(sk)
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1218-23
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Molecular basis for differential sensitivity of KCNQ and I(Ks) channels to the cognitive enhancer XE991.
pubmed:affiliation
Department of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York, Stony Brook, NY 11794-8661, USA. hswang@physiology.pnb.sunysb.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't