Function and regulation of taurine transport in Müller cells under osmotic stress

In the retina, taurine works as an osmolyte to exert a neuroprotective function, and it has been proposed that Müller cells, a major type of retinal glial cells, are involved in the osmolarity regulation of retinal neural cells by controlling the taurine concentration in retinal extracellular fluid (ECF). However, the detailed mechanism of taurine transport in Müller cells has not fully examined, and we investigated this using a conditionally immortalized rat Müller cell line (TR-MUL5 cells). In the uptake study, TR-MUL5 cells exhibited Na(+)-, Cl(-)-dependent [(3)H]taurine uptake with a K(m) of 37.9μM. The [(3)H]taurine uptake by TR-MUL5 cells was strongly inhibited by β-alanine and hypotaurine, substrates of taurine transporter TAUT (SLC6A6), and RT-PCR and immunoblot analyses demonstrated the expression of TAUT in Müller cells, suggesting the involvement of TAUT in taurine uptake by Müller cells. In the efflux study, [(3)H]taurine efflux by TR-MUL5 cells under hypotonic conditions was significantly greater than that under isotonic conditions, and significantly enhanced by sphingosine 1-phosphate (S1P), suggesting that the volume-sensitive taurine release is enhanced via G protein-coupled receptors (GPCRs) in Müller cells. Furthermore, [(3)H]taurine efflux by TR-MUL5 cells under hypotonic conditions was significantly inhibited in the presence of the volume-sensitive organic osmolyte and anion channel (VSOAC) inhibitor, suggesting a major contribution of VSOAC to the volume-sensitive taurine release by Müller cells. This is the first description of the detailed mechanism of taurine transport in Müller cells, indicating a possible function of Müller cells in retinal neuroprotection by regulating osmolarity of retinal ECF.