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Consequences of Impaired Gap Junctional Communication in Glial Cells

Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 468)

Abstract

Astrocytes are characterized by extensive gap junctional intercellular communication (GJIC) mediated by channels composed primarily of connexin43. To examine some of the functions of this intercellular communication in glial cells, we have used three approaches. The first involves transfection of glioma cells, which are deficient in connexin expression and gap junctional communication, with connexin cDNAs to examine changes in cellular phenotype following increased gap junctional communication. Using differential display, we have identified several genes which appear to be regulated by GJIC. The second is to study astrocytes cultured from embryonic mice with a null mutation in the connexin43 gene. These homozygous null astrocytes are devoid of connexin43 and also deficient in intercellular dye transfer. Markers of glial differentiation appear similar in all genotypes. Measurement of intercellular calcium concentration following mechanical stimulation of confluent astrocytes revealed that the number of cells affected by a rise in intracellular calcium was reduced in homozygous cultures compared to wild type. The growth rate of astrocytes lacking connexin43 was reduced compared to wild-type astrocytes. The third approach employs the use of gap junction blockers in a model of neuronal and glial differentiation, namely P19 mouse embryonal carcinoma cells treated with retinoic acid. In this case, blocking GJIC during the differentiation protocol prevents the appearance of neuronal and astrocytic phenotypes. Taken together, these data suggest an important role for GJIC in glial function and differentiation.

Keywords

Intercellular Communication Bystander Effect Glycyrrhizic Acid Glycyrrhetinic Acid Herpes Simplex Virus Thymidine Kinase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  1. 1.Department of Anatomy and Cell BiologyThe University of Western OntarioLondonCanada
  2. 2.Department of PsychiatryThe University of Western OntarioLondonCanada

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