Guanosine promotes the up‐regulation of inward rectifier potassium current mediated by Kir4.1 in cultured rat cortical astrocytes

Guanosine (Guo) is an endogenous neuroprotective molecule of the CNS, which has various acute and long‐term effects on both neurones and astroglial cells. Whether Guo also modulates the activity/expression of ion channels involved in homeostatic control of extracellular potassium by the astrocytic s...

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Bibliographic Details
Published in:Journal of neurochemistry 2006-07, Vol.98 (2), p.430-445
Main Authors: Benfenati, Valentina, Caprini, Marco, Nobile, Mario, Rapisarda, Carmela, Ferroni, Stefano
Format: Article
Language:English
Subjects:
Animals
Astrocytes - drug effects
Astrocytes - metabolism
astroglia
Biological and medical sciences
Blotting, Western
Brain
Brain research
Cells, Cultured
Cercopithecus aethiops
Cerebral Cortex - cytology
Cerebral Cortex - drug effects
Cerebral Cortex - metabolism
Chemistry
COS Cells
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
DNA, Complementary - biosynthesis
DNA, Complementary - genetics
Electrophysiology
Fundamental and applied biological sciences. Psychology
guanine‐based purines
Guanosine - pharmacology
Homeostasis
Immunoprecipitation
inward rectifier K+ channel
Ions
Isolated neuron and nerve. Neuroglia
Medical sciences
Membrane Proteins - biosynthesis
Membrane Proteins - genetics
Neurology
neuroprotection
Neuroprotective Agents
Patch-Clamp Techniques
pathophysiology
Potassium
potassium buffering
Potassium Channels, Inwardly Rectifying - biosynthesis
Potassium Channels, Inwardly Rectifying - physiology
Rats
Rodents
Transfection
Up-Regulation - drug effects
Vertebrates: nervous system and sense organs
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Summary:Guanosine (Guo) is an endogenous neuroprotective molecule of the CNS, which has various acute and long‐term effects on both neurones and astroglial cells. Whether Guo also modulates the activity/expression of ion channels involved in homeostatic control of extracellular potassium by the astrocytic syncytium is still unknown. Here we provide electrophysiological evidence that chronic exposure (48 h) to Guo (500 μm) promotes the functional expression of an inward rectifier K+ (Kir) conductance in primary cultured rat cortical astrocytes. Molecular screening indicated that Guo promotes the up‐regulation of the Kir4.1 channel, the major component of the Kir current in astroglia in vivo. Furthermore, the properties of astrocytic Kir current overlapped those of the recombinant Kir4.1 channel expressed in a heterologous system, strongly suggesting that the Guo‐induced Kir conductance is mainly gated by Kir4.1. In contrast, the expression levels of two other Kir channel proteins were either unchanged (Kir2.1) or decreased (Kir5.1). Finally, we showed that inhibition of translational process, but not depression of transcription, prevents the Guo‐induced up‐regulation of Kir4.1, indicating that this nucleoside acts through de novo protein synthesis. Because accumulating data indicate that down‐regulation of astroglial Kir current contributes to the pathogenesis of neurodegenerative diseases associated with dysregulation of extracellular K+ homeostasis, these results support the notion that Guo might be a molecule of therapeutic interest for counteracting the detrimental effect of K+‐buffering impairment of the astroglial syncytium that occurs in pathological conditions.
ISSN:0022-3042
1471-4159
DOI:10.1111/j.1471-4159.2006.03877.x