title: Electrophysiological alterations and upregulation of ATP receptors in retinal glial Müller cells from rats infected with the Borna disease virus.
abstract: Infection with the neurotropic Borna disease virus (BDV) causes an immune-mediated neurological disease in a broad range of species. In addition to encephalitis, BDV-infected Lewis rats develop a retinitis histologically characterized by the loss of most retinal neurons. By contrast, the dominating retinal macroglia, the Müller cells, do not degenerate. It is known from several models of neurodegeneration that glial cells may survive but undergo significant alterations of their physiological parameters. This prompted us to study the electrophysiology and ATP-induced changes of intracellular Ca(2+)-concentration ([Ca(2+)](i)) in Müller cells from BDV-infected rat retinae. Freshly isolated cells were used for whole-cell patch-clamp recordings. Whereas neither zero current potentials nor membrane resistances showed significant alterations, the membrane capacitance increased in cells from BDV-infected rats during survival times of up to 8 months. This process was accompanied by a decrease in K(+) current densities. Müller cells from BDV-infected rats were characterized by expression of a prominent fast-inactivating A-type K(+) current which was rarely found in control cells. Moreover, the number of cells displaying Na(+) currents was slightly increased after BDV-infection. ATP evoked increases in [Ca(2+)](i) in Müller cells within retinal wholemounts of both control and BDV-infected animals. However, the number of ATP-responding isolated cells increased from 24% (age-matched controls) to 78% (cells from animals > or =18 weeks after infection). We conclude that in BDV-induced retinopathy, reactive rat Müller cells change their physiological parameters but these changes are different from those in Müller cells during proliferative vitreoretinopathy in man and rabbit.
authors.affiliation: Paul-Flechsig-Institut für Hirnforschung, Universität Leipzig, Leipzig, Germany. pant@medizin.uni-leipzig.de
authors.forename: T
authors.initials: T
authors.lastname: Pannicke
authors.forename: M
authors.initials: M
authors.lastname: Weick
authors.forename: O
authors.initials: O
authors.lastname: Uckermann
authors.forename: T
authors.initials: T
authors.lastname: Wheeler-Schilling
authors.forename: J E
authors.initials: JE
authors.lastname: Fries
authors.forename: M B
authors.initials: MB
authors.lastname: Reichel
authors.forename: C
authors.initials: C
authors.lastname: Mohr
authors.forename: T
authors.initials: T
authors.lastname: Stahl
authors.forename: M
authors.initials: M
authors.lastname: Fluess
authors.forename: J
authors.initials: J
authors.lastname: Kacza
authors.forename: J
authors.initials: J
authors.lastname: Seeger
authors.forename: J A
authors.initials: JA
authors.lastname: Richt
authors.forename: A
authors.initials: A
authors.lastname: Reichenbach
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001890:Borna Disease / Q000821:virology*; D002118:Calcium / Q000378:metabolism; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D018048:Receptors, Purinergic P2 / Q000235:genetics; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D012160:Retina / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D012173:Retinitis / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D015222:Sodium Channels / Q000378:metabolism; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: C546384:P2ry1 protein, rat; C546387:P2ry2 protein, rat; D015221:Potassium Channels; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D015222:Sodium Channels; D001464:Barium; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine; D002118:Calcium