Developmental regulation of voltage-gated K+ channel and GABAA receptor expression in Bergmann glial cells.
Bergmann glial cells are closely associated with neurons: during development they provide guiding structures for migrating granule cells and in the adult cerebellum they display intimate interactions with Purkinje cells. In this study, we have addressed the question of whether such changes in neuronal-glial interactions during development are accompanied by variations in the membrane properties of Bergmann glial cells. We used a mouse cerebellum slice preparation to study membrane currents of the Bergmann glial cells at various stages of development in situ using the patch-clamp technique. The distinct morphology of Bergmann glial cells was revealed by Lucifer yellow injections during recording. While Bergmann glial cells in mice of postnatal day 20 (P20) to P30 have thick processes with arborized, irregularly shaped leaf-like appendages, the processes of cells from younger mice (P5-P7) are thinner and smoother. This morphological maturation is accompanied by a variation in voltage-gated currents. In cells from P5 to P7, delayed outward- and inward-rectifying K+ currents were recorded, while older Bergmann glial cells were characterized by, large, voltage- and time-independent K+ currents. In addition, application of GABA induces two effects, a rapid activation of a Cl- conductance and a longer-lasting decrease in the (resting) K+ conductance. Both effects were mediated by benzodiazepine-insensitive GABAA receptors. Responses in cells of P5-P7 mice were large as compared to the small or even undetectable responses in P20-P30 cells. These GABAA receptors were characterized immunohistochemically in mice and rat brain sections with five subunit-specific antibodies. Bergmann glial cells exhibit a distinct but transient immunoreactivity for the GABAA receptor alpha 2-, alpha 3-, and delta-subunits. Staining is maximal between P7 and P10 and decreases gradually thereafter. In contrast, antibodies to the alpha 1- and beta 2,3-subunits fail to decorate Bergmann glial cells, although they yield a prominent staining of both the Purkinje cells and the granule cells. These changes in the Bergmann glial cell membrane properties and GABAA receptor expression suggest a transition between functional states during development of the Bergmann glial cells.
Müller
T
T
Department of Neurobiology, University of Heidelberg, Germany.
Fritschy
J M
JM
Grosche
J
J
Pratt
G D
GD
Möhler
H
H
Kettenmann
H
H
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015221:Potassium Channels / Q000032:analysis / Q000096:biosynthesis* / Q000502:physiology; D011963:Receptors, GABA-A / Q000032:analysis / Q000096:biosynthesis* / Q000502:physiology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D005904:Glial Fibrillary Acidic Protein; D015221:Potassium Channels; D011963:Receptors, GABA-A; D013757:Tetraethylammonium Compounds; D001464:Barium; D005680:gamma-Aminobutyric Acid; D019789:Tetraethylammonium; D001640:Bicuculline