Pharmacological characterization of swelling-induced D-[3H]aspartate release from primary astrocyte cultures

Eric M. Rutledge, Michael Aschner, Harold K. Kimelberg

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

During stroke or head trauma, extracellular K+ concentration increases, which can cause astrocytes to swell. In vitro, such swelling causes astrocytes to release excitatory amino acids, which may contribute to excitotoxicity in vivo. Several putative swelling-activated channels have been identified through which such anionic organic cellular osmolytes can be released. In the present study, we sought to identify the swelling-activated channel(s) responsible for D-[3H]aspartate release from primary cultured astrocytes exposed to either KCl or hypotonic medium. KCl-induced D- [3H]aspartate release was inhibited by the anion channel inhibitors 5- nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), dideoxyforskolin, L- 644711, ATP, ITP, 3'-azido-3'-deoxythymidine, DIDS, and tamoxifen but not by cAMP. The cell swelling caused by raised KCl was not inhibited by extracellular ATP or tamoxifen as measured by an electrical impedance method, which suggests that these anion channel inhibitors directly blocked the channel responsible for efflux. Extracellular nucleotides and DIDS, however, had no or only partial effects on D-[3H]aspartate release from cells swollen by hypotonic medium, but such release was inhibited by NPPB, dideoxyforskolin, and tamoxifen. Of the swelling-activated channels so far identified, our data suggest that a volume-sensitive outwardly rectifying channel is responsible for D-[3H]aspartate release from primary cultured astrocytes during raised extracellular K+ and possibly during hypotonic medium-induced release.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume274
Issue number6 43-6
StatePublished - Jun 1998
Externally publishedYes

Fingerprint

D-Aspartic Acid
Aspartic Acid
Astrocytes
Swelling
Tamoxifen
Pharmacology
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
L 644711
Anions
Adenosine Triphosphate
Inosine Triphosphate
Excitatory Amino Acids
Benzoic Acid
Zidovudine
Electric Impedance
Craniocerebral Trauma
Acoustic impedance
Nucleotides
Stroke

Keywords

  • 5-nitro- 2-(3-phenylpropylamino)benzoic acid
  • Excitatory amino acids
  • Extracellular ATP
  • Swelling-activated anion channels
  • Tamoxifen
  • Volume-sensing outwardly rectifying channel

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Pharmacological characterization of swelling-induced D-[3H]aspartate release from primary astrocyte cultures. / Rutledge, Eric M.; Aschner, Michael; Kimelberg, Harold K.

In: American Journal of Physiology - Cell Physiology, Vol. 274, No. 6 43-6, 06.1998.

Research output: Contribution to journalArticle

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