Requirement of functional ryanodine receptor type 3 for astrocyte migration

FASEB J. 2002 Jan;16(1):84-6. doi: 10.1096/fj.01-0380fje. Epub 2001 Nov 14.

Abstract

Astrocyte motility plays an important role in the response of the brain to injury and during regeneration. We used two in vitro assays, a wound-healing model and a chemotaxis assay, to study mechanisms that control astrocyte motility. Ryanodine receptors (RyR), intracellular calcium-release channels, modulate intracellular Ca2+ levels, and also motility: 1) blocking RyR with antagonizing concentration of ryanodine (200 microM) strongly attenuated motility and 2) motility of astrocytes cultured from homozygous RyR type 3 knockout mice was impaired strongly compared with wild-type. In contrast, MIP-1a-induced chemotaxis was neither impaired in the presence of ryanodine nor in the cells from the knockout animals. Reverse transcription-polymerase chain reaction (RT-PCR) analysis combined with Western blotting and immunocytochemistry confirmed the expression of RyR type 3, but not type 1 or 2 in cultured and acutely isolated astrocytes. RyR in astrocytes are linked to Ca2+ signaling because the RyR agonist 4-chloro-m-cresol induced a release of Ca2+ from intracellular stores. These results indicate that astrocytes express only RyR type 3 and that this receptor is important for controlling astrocyte motility.

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / physiology*
  • Brain / metabolism
  • Calcium / metabolism
  • Cell Movement* / drug effects
  • Cells, Cultured
  • Chemotaxis
  • Mice
  • Mice, Knockout
  • Models, Biological
  • RNA, Messenger / biosynthesis
  • Ryanodine / pharmacology
  • Ryanodine Receptor Calcium Release Channel / genetics
  • Ryanodine Receptor Calcium Release Channel / physiology*

Substances

  • RNA, Messenger
  • Ryanodine Receptor Calcium Release Channel
  • Ryanodine
  • Calcium

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