Mechanisms of enhanced taurine release under Ca2+ depletion

The sulfur-containing amino acid taurine is an inhibitory neuromodulator in the brain of mammals, as well as a key substance in the regulation of cell volumes. The effect of Ca2+ on extracellular taurine concentrations is of special interest in the context of the regulatory mechanisms of taurine release. The aim of this study was to characterize the basal release of taurine in Ca2+-free medium using in vivo microdialysis of the striatum of anesthetized rats. Perfusion of Ca2+-free medium via a microdialysis probe evoked a sustained release of taurine (up to 180 % compared to the basal levels). The Ca2+ chelator EGTA (1 mM) potentiated Ca2+ depletion-evoked taurine release. The substitution of CaCl2 by choline chloride did not alter the observed effect. Ca2+-free solution did not significantly evoke release of taurine from tissue loaded with the competitive inhibitor of taurine transporter guanidinoethanesulfonate (1 mM), suggesting that in Ca2+ depletion taurine is released by the transporter operating in the outward direction. The volume-sensitive chloride channel blocker diisothiocyanostilbene-2,2′-disulfonate (1 mM) did not attenuate the taurine release evoked by Ca2+ depletion. The non-specific blocker of voltage-sensitive Ca2+ channels NiCl2 (0.65 mM) enhanced taurine release in the presence of Ca2+. CdCl2 (0.25 mM) had no effect under these conditions. However, both CdCl2 and NiCl2 attenuated the effect of Ca2+-free medium on the release of taurine. The data obtained imply the involvement of both decreased influx of Ca2+ and increased non-specific influx of Na+ through voltage-sensitive calcium channels in the regulation of transporter-mediated taurine release in Ca2+ depletion.