Pharmacological characterization of volume-sensitive, taurine permeable anion channels in rat supraoptic glial cells

Br J Pharmacol. 2000 Aug;130(8):1976-82. doi: 10.1038/sj.bjp.0703492.

Abstract

To characterize the volume-sensitive, osmolyte permeable anion channels responsible for the osmodependent release of taurine from supraoptic nucleus (SON) astrocytes, we investigated the pharmacological properties of the [(3)H]-taurine efflux from acutely isolated SON. Taurine release induced by hypotonic stimulus (250 mosmol l(-1)) was not antagonized by the taurine transporter blocker guanidinoethyl sulphonate, confirming the lack of implication of the transporter. The osmodependent release of taurine was blocked by a variety of Cl(-) channel inhibitors with the order of potency: NPPB>niflumic acid>DPC>DIDS>ATP. On the other hand, release of taurine was only weakly affected by other compounds (dideoxyforskolin, 4-bromophenacyl bromide, mibefradil) known to block volume-activated anion channels in other cell preparations, and was completely insensitive to tamoxifen, a broad inhibitor of these channels. Although the molecular identity of volume-sensitive anion channels is not firmly established, a few genes have been postulated as potential candidates to encode such channels. We checked the expression in the SON of three of them, ClC(3), phospholemman and VDAC(1), and found that the transcripts of these genes are found in SON neurons, but not in astrocytes. Similar observation was previously reported for ClC(2). In conclusion, the osmodependent taurine permeable channels of SON astrocytes display a particular pharmacological profile, suggesting the expression of a particular type or subtype of volume-sensitive anion channel, which is likely to be formed by yet unidentified proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
  • Acetophenones / pharmacology
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Calcium Channel Blockers / pharmacology
  • Chloride Channels / drug effects
  • Chloride Channels / genetics
  • Colforsin / analogs & derivatives*
  • Colforsin / pharmacology
  • Diffusion
  • Dose-Response Relationship, Drug
  • Gene Expression
  • In Situ Hybridization
  • Ion Channels / drug effects*
  • Ion Channels / genetics
  • Male
  • Mibefradil / pharmacology
  • Neuroglia / cytology
  • Neuroglia / drug effects*
  • Neuroglia / metabolism
  • Niflumic Acid / pharmacology
  • Nitrobenzoates / pharmacology
  • Osmotic Pressure
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Supraoptic Nucleus / cytology
  • Supraoptic Nucleus / drug effects*
  • Supraoptic Nucleus / metabolism
  • Tamoxifen / pharmacology
  • Taurine / metabolism*
  • ortho-Aminobenzoates / pharmacology

Substances

  • Acetophenones
  • Calcium Channel Blockers
  • Chloride Channels
  • Ion Channels
  • Nitrobenzoates
  • RNA, Messenger
  • ortho-Aminobenzoates
  • Tamoxifen
  • Taurine
  • Colforsin
  • Mibefradil
  • 5-nitro-2-(3-phenylpropylamino)benzoic acid
  • Niflumic Acid
  • Adenosine Triphosphate
  • fenamic acid
  • 1,9-dideoxyforskolin
  • 4-bromophenacyl bromide
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid