title: Neuroinflammation alters voltage-dependent conductance in striatal astrocytes.
abstract: Neuroinflammation has the capacity to alter normal central nervous system (CNS) homeostasis and function. The objective of the present study was to examine the effects of an inflammatory milieu on the electrophysiological properties of striatal astrocyte subpopulations with a mouse bacterial brain abscess model. Whole cell patch-clamp recordings were performed in striatal glial fibrillary acidic protein (GFAP)-green fluorescent protein (GFP)(+) astrocytes neighboring abscesses at postinfection days 3 or 7 in adult mice. Cell input conductance (G(i)) measurements spanning a membrane potential (V(m)) surrounding resting membrane potential (RMP) revealed two prevalent astrocyte subsets. A1 and A2 astrocytes were identified by negative and positive G(i) increments vs. V(m), respectively. A1 and A2 astrocytes displayed significantly different RMP, G(i), and cell membrane capacitance that were influenced by both time after bacterial exposure and astrocyte proximity to the inflammatory site. Specifically, the percentage of A1 astrocytes was decreased immediately surrounding the inflammatory lesion, whereas A2 cells were increased. These changes were particularly evident at postinfection day 7, revealing increased cell numbers with an outward current component. Furthermore, RMP was inversely modified in A1 and A2 astrocytes during neuroinflammation, and resting G(i) was increased from 21 to 30 nS in the latter. In contrast, gap junction communication was significantly decreased in all astrocyte populations associated with inflamed tissues. Collectively, these findings demonstrate the heterogeneity of striatal astrocyte populations, which experience distinct electrophysiological modifications in response to CNS inflammation.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-5900, USA.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Karpuk
authors.forename: Maria
authors.initials: M
authors.lastname: Burkovetskaya
authors.forename: Tammy
authors.initials: T
authors.lastname: Kielian
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000145:classification / Q000473:pathology / Q000502:physiology*; D001703:Biophysics; D001922:Brain Abscess / Q000150:complications; D003342:Corpus Striatum / Q000473:pathology*; D004558:Electric Stimulation; D004660:Encephalitis / Q000209:etiology* / Q000473:pathology*; D017629:Gap Junctions / Q000187:drug effects / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D016014:Linear Models; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D013203:Staphylococcal Infections / Q000150:complications; D013997:Time Factors
chemical_list: D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins