Linked Life Data

19675305

Source:http://linkedlifedata.com/resource/pubmed/id/19675305

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-10-29
pubmed:abstractText
Kv4.3, with its complex open- and closed-state inactivation (CSI) characteristics, is a primary contributor to early cardiac repolarization. The two alternatively spliced forms, Kv4.3-short (Kv4.3-S) and Kv4.3-long (Kv4.3-L), differ by the presence of a 19-amino acid insert downstream from the sixth transmembrane segment. The isoforms are similar kinetically; however, the longer form has a unique PKC phosphorylation site. To test the possibility that inactivation is differentially regulated by phosphorylation, we expressed the Kv4.3 isoforms in Xenopus oocytes and examined changes in their inactivation properties after stimulation of PKC activity. Whereas there was no difference in open-state inactivation, there were profound differences in CSI. In Kv4.3-S, PMA reduced the magnitude of CSI by 24% after 14.4 s at -50 mV. In contrast, the magnitude of CSI in Kv4.3-L increased by 25% under the same conditions. Mutation of a putatively phosphorylated threonine (T504) to aspartic acid within a PKC consensus recognition sequence unique to Kv4.3-L eliminated the PMA response. The change in CSI was independent of the intervention used to increase PKC activity; identical results were obtained with either PMA or injected purified PKC. Our previously published 11-state model closely simulated our experimental data. Our data demonstrate isoform-specific regulation of CSI by PKC in Kv4.3 and show that the carboxy terminus of Kv4.3 plays an important role in regulation of CSI.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1522-1563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
297
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C1236-48
pubmed:dateRevised
2010-11-2
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Closed-state inactivation in Kv4.3 isoforms is differentially modulated by protein kinase C.
pubmed:affiliation
Key Laboratory of Molecular Biophysics, Huazhong University of Science and Technology, Ministry of Education, College of Life Science and Technology, Wuhan, Hubei, China.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural