Linked Life Data

11027211

Source:http://linkedlifedata.com/resource/pubmed/id/11027211

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2000-10-16
pubmed:abstractText
We have recently disrupted Slc12a2, the gene encoding the secretory Na-K-2Cl cotransporter in mice (NKCC1) (Delpire et al., 1999). Gramicidin perforated-patch and whole-cell recordings were performed to study GABA-induced currents in dorsal root ganglion (DRG) neurons isolated from wild-type and homozygote NKCC1 knock-out mice. In wild-type DRG neurons, strong GABA-evoked inward current was observed at the resting membrane potential, suggesting active accumulation of Cl(-) in these cells. This GABA-induced current was blocked by picrotoxin, a GABA(A) receptor blocker. The strong Cl(-) accumulation that gives rise to depolarizing GABA responses is caused by Na-K-2Cl cotransport because reduction of external Cl(-) or application of bumetanide induced a decrease in [Cl(-)](i), whereas an increase in external K(+) caused an apparent [Cl(-)](i) accumulation. In contrast to control neurons, little or no net current was observed at the resting membrane potential in homozygote NKCC1 mutant DRG neurons. E(GABA) was significantly more negative, demonstrating the absence of Cl(-) accumulation in these cells. Application of bumetanide induced a positive shift of E(GABA), suggesting the presence of an outward Cl(-) transport mechanism. In agreement with an absence of GABA depolarization in DRG neurons, behavioral analysis revealed significant alterations in locomotion and pain perception in the knock-out mouse. Our results clearly demonstrate that the Na-K-2Cl cotransporter is responsible for [Cl(-)](i) accumulation in DRG neurons and that via regulation of intracellular Cl(-), the Na-K-2Cl cotransporter participates in the modulation of GABA neurotransmission and sensory perception.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7531-8
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:11027211-Animals, pubmed-meshheading:11027211-Behavior, Animal, pubmed-meshheading:11027211-Bumetanide, pubmed-meshheading:11027211-Carrier Proteins, pubmed-meshheading:11027211-Cells, Cultured, pubmed-meshheading:11027211-Chlorides, pubmed-meshheading:11027211-Female, pubmed-meshheading:11027211-GABA Antagonists, pubmed-meshheading:11027211-GABA-A Receptor Antagonists, pubmed-meshheading:11027211-Gait Disorders, Neurologic, pubmed-meshheading:11027211-Ganglia, Spinal, pubmed-meshheading:11027211-Gramicidin, pubmed-meshheading:11027211-Male, pubmed-meshheading:11027211-Membrane Potentials, pubmed-meshheading:11027211-Mice, pubmed-meshheading:11027211-Mice, Knockout, pubmed-meshheading:11027211-Neurons, pubmed-meshheading:11027211-Pain Measurement, pubmed-meshheading:11027211-Patch-Clamp Techniques, pubmed-meshheading:11027211-Picrotoxin, pubmed-meshheading:11027211-Potassium, pubmed-meshheading:11027211-Receptors, GABA-A, pubmed-meshheading:11027211-Sodium-Potassium-Chloride Symporters, pubmed-meshheading:11027211-gamma-Aminobutyric Acid
pubmed:year
2000
pubmed:articleTitle
Abnormal GABAA receptor-mediated currents in dorsal root ganglion neurons isolated from Na-K-2Cl cotransporter null mice.
pubmed:affiliation
Departments of Anesthesiology, Center for Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, Tennesse, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't