Neuroinflammation leads to region-dependent alterations in astrocyte gap junction communication and hemichannel activity

Nikolay Karpuk, Maria Burkovetskaya, Teresa Fritz, Amanda Angle, Tammy L Kielian

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Inflammation attenuates gap junction (GJ) communication in cultured astrocytes. Here we used a well-characterized model of experimental brain abscess as a tool to query effects of the CNS inflammatory milieu on astrocyte GJ communication and electrophysiological properties. Whole-cell patch-clamp recordings were performed on green fluorescent protein (GFP)-positive astrocytes in acute brain slices from glial fibrillary acidic protein-GFP mice at 3 or 7 d after Staphylococcus aureus infection in the striatum. Astrocyte GJ communication was significantly attenuated in regions immediately surrounding the abscess margins and progressively increased to levels typical of uninfected brain with increasing distance from the abscess proper. Conversely, astrocytes bordering the abscess demonstrated hemichannel activity as evident by enhanced ethidium bromide (EtBr) uptake that could be blocked by several pharmacological inhibitors, including the connexin 43 (Cx43) mimetic peptide Gap26, carbenoxolone, the pannexin1 (Panx1) mimetic peptide 10Panx1, and probenecid. However, hemichannel opening was transient with astrocytic EtBr uptake observed near the abscess at day 3 but not day 7 after infection. The region-dependent pattern of hemichannel activity at day 3 directly correlated with increases in Cx43, Cx30, Panx1, and glutamate transporter expression (glial L-glutamate transporter and L-glutamate/L-aspartate transporter) along the abscess margins. Changes in astrocyte resting membrane potential and input conductance correlated with the observed changes in GJ communication and hemichannel activity. Collectively, these findings indicate that astrocyte coupling and electrical properties are most dramatically affected near the primary inflammatory site and reveal an opposing relationship between the open states of GJ channels versus hemichannels during acute infection. This relationship may extend to other CNS diseases typified with an inflammatory component.

Original languageEnglish (US)
Pages (from-to)414-425
Number of pages12
JournalJournal of Neuroscience
Volume31
Issue number2
DOIs
StatePublished - Jan 12 2011

Fingerprint

Gap Junctions
Astrocytes
Communication
Abscess
Amino Acid Transport System X-AG
Connexin 43
Ethidium
Green Fluorescent Proteins
Glutamic Acid
Infection
Carbenoxolone
Probenecid
Brain Abscess
Central Nervous System Diseases
Glial Fibrillary Acidic Protein
Brain
Aspartic Acid
Neuroglia
Membrane Potentials
Staphylococcus aureus

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Neuroinflammation leads to region-dependent alterations in astrocyte gap junction communication and hemichannel activity. / Karpuk, Nikolay; Burkovetskaya, Maria; Fritz, Teresa; Angle, Amanda; Kielian, Tammy L.

In: Journal of Neuroscience, Vol. 31, No. 2, 12.01.2011, p. 414-425.

Research output: Contribution to journalArticle

Karpuk, Nikolay ; Burkovetskaya, Maria ; Fritz, Teresa ; Angle, Amanda ; Kielian, Tammy L. / Neuroinflammation leads to region-dependent alterations in astrocyte gap junction communication and hemichannel activity. In: Journal of Neuroscience. 2011 ; Vol. 31, No. 2. pp. 414-425.
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