Linked Life Data

9727001

Source:http://linkedlifedata.com/resource/pubmed/id/9727001

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
37
pubmed:dateCreated
1998-10-13
pubmed:databankReference
pubmed:abstractText
Loss of function mutations in kidney Kir1.1 (renal outer medullary potassium channel, KCNJ1) inwardly rectifying potassium channels can be found in patients suffering from hyperprostaglandin E syndrome (HPS), the antenatal form of Bartter syndrome. A novel mutation found in a sporadic case substitutes an asparagine by a positively charged lysine residue at amino acid position 124 in the extracellular M1-H5 linker region. When heterologously expressed in Xenopus oocytes and mammalian cells, current amplitudes from mutant Kir1.1a[N124K] channels were reduced by a factor of approximately 12 as compared with wild type. A lysine at the equivalent position is present in only one of the known Kir subunits, the newly identified Kir1.3, which is also poorly expressed in the recombinant system. When the lysine residue in guinea pig Kir1.3 (gpKir1.3) isolated from a genomic library was changed to an asparagine (reverse HPS mutation), mutant channels yielded macroscopic currents with amplitudes increased 6-fold. From single channel analysis it became apparent that the decrease in mutant Kir1.1 channels and the increase in mutant gpKir1.3 macroscopic currents were mainly due to the number of expressed functional channels. Coexpression experiments revealed a dominant-negative effect of Kir1.1a[N124K] and gpKir1.3 on macroscopic current amplitudes when coexpressed with wild type Kir1.1a and gpKir[K110N], respectively. Thus we postulate that in Kir1.3 channels the extracellular positively charged lysine is of crucial functional importance. The HPS phenotype in man can be explained by the lower expression of functional channels by the Kir1. 1a[N124K] mutant.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23884-91
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9727001-Amino Acid Sequence, pubmed-meshheading:9727001-Animals, pubmed-meshheading:9727001-Bartter Syndrome, pubmed-meshheading:9727001-COS Cells, pubmed-meshheading:9727001-Cloning, Molecular, pubmed-meshheading:9727001-Female, pubmed-meshheading:9727001-Humans, pubmed-meshheading:9727001-Kidney Medulla, pubmed-meshheading:9727001-Molecular Sequence Data, pubmed-meshheading:9727001-Mutagenesis, Site-Directed, pubmed-meshheading:9727001-Oocytes, pubmed-meshheading:9727001-Point Mutation, pubmed-meshheading:9727001-Polymerase Chain Reaction, pubmed-meshheading:9727001-Polymorphism, Single-Stranded Conformational, pubmed-meshheading:9727001-Potassium Channels, pubmed-meshheading:9727001-Potassium Channels, Inwardly Rectifying, pubmed-meshheading:9727001-Prostaglandins E, pubmed-meshheading:9727001-Recombinant Proteins, pubmed-meshheading:9727001-Sequence Alignment, pubmed-meshheading:9727001-Sequence Homology, Amino Acid, pubmed-meshheading:9727001-Syndrome, pubmed-meshheading:9727001-Transfection, pubmed-meshheading:9727001-Xenopus laevis
pubmed:year
1998
pubmed:articleTitle
A hyperprostaglandin E syndrome mutation in Kir1.1 (renal outer medullary potassium) channels reveals a crucial residue for channel function in Kir1.3 channels.
pubmed:affiliation
Institute for Physiology, Philipps University, 35033 Marburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't