IN order to investigate GABA uptake into Muller glial cells electrophysiologically, we used the whole-cell voltage-clamp technique. Since Muller cells were insensitive to application of muscimol and baclofen, the expression of GABA(A) and GABA(B) receptors can be excluded. Therefore, the observed GABA current must be due to an electrogenic GABA transporter. This transporter is driven by the transmembrane Na+ gradient, as replacement of the extracellular Na+ by choline inhibits the GABA current. Currents evoked by cis-4-aminocrotonic acid, a GABA(C) specific agonist, are also inhibited by replacement of extracellular Na+, indicating that this compound is a substrate for the uptake. The competitive GABA uptake blockers p-alanine and nipecotic acid are substrates of the transporter as well, and produce 42% and 65% of the currents elicited by the same GABA concentration, respectively. Affinity of the transporter for GABA is high, the K-m value being 5 mu M at -80 mV.