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PMID:17942730

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Citation

Djukic, B, Casper, KB, Philpot, BD, Chin, LS and McCarthy, KD (2007) Conditional knock-out of Kir4.1 leads to glial membrane depolarization, inhibition of potassium and glutamate uptake, and enhanced short-term synaptic potentiation. J. Neurosci. 27:11354-65

Abstract

During neuronal activity, extracellular potassium concentration ([K+]out) becomes elevated and, if uncorrected, causes neuronal depolarization, hyperexcitability, and seizures. Clearance of K+ from the extracellular space, termed K+ spatial buffering, is considered to be an important function of astrocytes. Results from a number of studies suggest that maintenance of [K+]out by astrocytes is mediated by K+ uptake through the inward-rectifying Kir4.1 channels. To study the role of this channel in astrocyte physiology and neuronal excitability, we generated a conditional knock-out (cKO) of Kir4.1 directed to astrocytes via the human glial fibrillary acidic protein promoter gfa2. Kir4.1 cKO mice die prematurely and display severe ataxia and stress-induced seizures. Electrophysiological recordings revealed severe depolarization of both passive astrocytes and complex glia in Kir4.1 cKO hippocampal slices. Complex cell depolarization appears to be a direct consequence of Kir4.1 removal, whereas passive astrocyte depolarization seems to arise from an indirect developmental process. Furthermore, we observed a significant loss of complex glia, suggestive of a role for Kir4.1 in astrocyte development. Kir4.1 cKO passive astrocytes displayed a marked impairment of both K+ and glutamate uptake. Surprisingly, membrane and action potential properties of CA1 pyramidal neurons, as well as basal synaptic transmission in the CA1 stratum radiatum appeared unaffected, whereas spontaneous neuronal activity was reduced in the Kir4.1 cKO. However, high-frequency stimulation revealed greatly elevated posttetanic potentiation and short-term potentiation in Kir4.1 cKO hippocampus. Our findings implicate a role for glial Kir4.1 channel subunit in the modulation of synaptic strength.

Links

PubMed Online version:10.1523/JNEUROSCI.0723-07.2007

Keywords

Animals; Cell Membrane/metabolism; Cell Membrane/physiology; Glutamic Acid/metabolism; Membrane Potentials/genetics; Membrane Potentials/physiology; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Neuroglia/metabolism; Neuroglia/physiology; Potassium/antagonists & inhibitors; Potassium/metabolism; Potassium Channels, Inwardly Rectifying/deficiency; Potassium Channels, Inwardly Rectifying/genetics; Potassium Channels, Inwardly Rectifying/physiology; Protein Subunits/deficiency; Protein Subunits/genetics; Protein Subunits/physiology; Synaptic Transmission/genetics; Synaptic Transmission/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:KCJ10

acts_upstream_of_or_within

GO:0022010: central nervous system myelination

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3655847,MGI:MGI:3761690

P

  • occurs_in:(EMAPA:35235)|occurs_in:(EMAPA:35253)|occurs_in:(EMAPA:35187)|occurs_in:(EMAPA:17540)

Seeded From UniProt

complete

MOUSE:KCJ10

acts_upstream_of_or_within

GO:0007628: adult walking behavior

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3655847,MGI:MGI:3761690

P

Seeded From UniProt

complete

MOUSE:KCJ10

acts_upstream_of_or_within

GO:0014003: oligodendrocyte development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3655847,MGI:MGI:3761690

P

  • occurs_in:(EMAPA:35235)|occurs_in:(EMAPA:35253)|occurs_in:(EMAPA:35187)|occurs_in:(EMAPA:17540)

Seeded From UniProt

complete

MOUSE:KCJ10

acts_upstream_of_or_within

GO:0051935: glutamate reuptake

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3655847,MGI:MGI:3761690

P

  • occurs_in:(CL:0000127)
  • occurs_in:(EMAPA:32845)

Seeded From UniProt

complete

MOUSE:KCJ10

acts_upstream_of_or_within

GO:0048169: regulation of long-term neuronal synaptic plasticity

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3655847,MGI:MGI:3761690

P

  • occurs_in:(EMAPA:32845)

Seeded From UniProt

complete

MOUSE:KCJ10

acts_upstream_of_or_within

GO:0060075: regulation of resting membrane potential

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3655847,MGI:MGI:3761690

P

  • occurs_in:(CL:0000128)
  • occurs_in:(EMAPA:35253)|occurs_in:(CL:0000127)
  • occurs_in:(EMAPA:32845)

Seeded From UniProt

complete

MOUSE:KCJ10

acts_upstream_of_or_within

GO:0055075: potassium ion homeostasis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3655847,MGI:MGI:3761690

P

Seeded From UniProt

complete


See also

References

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