Kir4.1 channels mediate a depolarization of hippocampal astrocytes under hyperammonemic conditions in situ

Autor: Christian Steinhäuser, Karl W. Kafitz, Christine R. Rose, Daniel Koch, Simone Durry, Peter Hochstrate, Nicole Haack, Gerald Seifert, Jonathan Stephan
Rok vydání: 2012
Předmět:
Patch-Clamp Techniques
Biophysics
Tetrodotoxin
In Vitro Techniques
Biology
Hippocampus
Ouabain
Membrane Potentials
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Sodium Potassium Chloride Symporter Inhibitors
Ammonia
Furosemide
Glial Fibrillary Acidic Protein
Potassium Channel Blockers
Extracellular
medicine
Animals
Patch clamp
Potassium Channels
Inwardly Rectifying
Bumetanide
030304 developmental biology
Mice
Knockout
Mice
Inbred BALB C
0303 health sciences
Dose-Response Relationship
Drug
Age Factors
Glutamate receptor
Tetraethylammonium
Depolarization
Electric Stimulation
Potassium channel
Mice
Inbred C57BL
Quaternary Ammonium Compounds
medicine.anatomical_structure
Animals
Newborn
Neurology
Biochemistry
Astrocytes
Potassium
Excitatory Amino Acid Antagonists
030217 neurology & neurosurgery
Homeostasis
Sodium Channel Blockers
medicine.drug
Astrocyte
Zdroj: Glia; Vol 60
Glia
ISSN: 0894-1491
DOI: 10.1002/glia.22328
Popis: Increased ammonium (NH(4) (+) ) concentration in the brain is the prime candidate responsible for hepatic encephalopathy (HE), a serious neurological disorder caused by liver failure and characterized by disturbed glutamatergic neurotransmission and impaired glial function. We investigated the mechanisms of NH(4) (+) -induced depolarization of astrocytes in mouse hippocampal slices using whole-cell patch-clamp and potassium-selective microelectrodes. At postnatal days (P) 18-21, perfusion with 5 mM NH(4) (+) evoked a transient increase in the extracellular potassium concentration ([K(+) ](o) ) by about 1 mM. Astrocytes depolarized by on average 8 mV and then slowly repolarized to a plateau depolarization of 6 mV, which was maintained during NH(4) (+) perfusion. In voltage-clamped astrocytes, NH(4) (+) induced an inward current and a reduction in membrane resistance. Amplitudes of [K(+) ](o) transients and astrocyte depolarization/inward currents increased from P3-4 to P18-21. Perfusion with 100 μM Ba(2+) did not alter [K(+) ](o) transients but strongly reduced both astrocyte depolarization and inward currents. NH(4) (+) -induced depolarization and inward currents were also virtually absent in slices from Kir4.1 -/- mice, while [K(+) ](o) transients were unaltered. Blocking Na(+) /K(+) -ATPase with ouabain caused an immediate and complex increase in [K(+) ](o) . Taken together, our results are in agreement with the hypothesis that reduced uptake of K(+) by the Na(+) , K(+) -ATPase in the presence of NH(4) (+) disturbs the extracellular K(+) homeostasis. Furthermore, astrocytes depolarize in response to the increase in [K(+) ](o) and by influx of NH(4) (+) through Kir4.1 channels. The depolarization reduces the astrocytes' capacity for channel-mediated flux of K(+) and for uptake of glutamate and might hereby contribute to the pathology of HE.
Databáze: OpenAIRE
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