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

Abstract

1 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 e ux from acutely isolated SON. 2 Taurine release induced by hypotonic stimulus (250 mosmol l 71 ) was not antagonized by the taurine transporter blocker guanidinoethyl sulphonate, con®rming the lack of implication of the transporter. 3 The osmodependent release of taurine was blocked by a variety of Cl 7 channel inhibitors with the order of potency: NPPB4ni¯umic acid4DPC4DIDS4ATP. On the other hand, release of taurine was only weakly a ected 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. 4 Although the molecular identity of volume-sensitive anion channels is not ®rmly 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 . 5 In conclusion, the osmodependent taurine permeable channels of SON astrocytes display a particular pharmacological pro®le, suggesting the expression of a particular type or subtype of volume-sensitive anion channel, which is likely to be formed by yet unidenti®ed proteins.

Chloride/anion channels in glial cell membranes

“…This efflux was not due to unspecific leakage from the cells. However, the discrepancy of the results reported by Bres et al (2000) and Stegen et al (2000) might be explained by the possibility that the overexpression of these channels in oocytes leads to the expression of an unrelated taurine pathway.…”

“…The underlying genes for these channels remain to be identified (Jentsch et al, 2002). Neither ClC-2 nor ClC-3 genes appear to code for this channel family in situ (Bres et al, 2000). However, Stegen et al (2000) found CLC-2 and -3 expressed in cultured rat astrocytes.…”

Osmoregulation of Taurine Efflux from Cultured Human Breast Cancer Cells: Comparison with Volume Activated Cl^- Efflux and Regulation by Extracellular ATP

“…Other studies have suggested that volumesensitive taurine efflux does not always utilize anion channels. It is apparent that taurine efflux in Ehrlich Ascites cells [7], lactating rat mammary tissue [8,9], skate erythrocytes [23], supraoptic glial cells [24], C6 glioma cells [25] and cultured human intestinal epithelial cells [26] is independent from volume-activated chloride channels. It is also claimed that volume-activated taurine efflux from some cell types is via an anion exhanger [27].…”

Taurine Is a Potent Activator of Extrasynaptic GABAAReceptors in the Thalamus

“…In the brain, taurine has been reported to be released in response to hypo-osmotic stimulation, energy deprivation, and membrane depolarization (Oja and Saransaari, 2000). Taurine can be released from glia (Holopainen et al, 1989;Philibert et al, 1989;Koyama et al, 1994;Bres et al, 2000) and neurons (Holopainen et al, 1989;Schousboe and Pasantes-Morales, 1989;Van Vliet et al, 1989), and the release mechanisms appear to involve volume-sensitive anion channels (Hussy et al, 2001) and taurine transporters (Saransaari and Oja, 1999). Several lines of evidence indicate that extrasynaptic GABA A -Rs are the principal site of action for taurine in the thalamus.…”