GABA(A) receptors in Müller glial cells of the human retina.

The present study was aimed at characterizing the GABA(A) receptor-mediated currents in acutely isolated glial (Müller) cells of the human retina and investigating their subcellular localization across the Müller cell membrane. Extracellular application of GABA evoked two current responses in human Müller cells: a fast transient GABA(A) receptor-mediated current that inactivated within 10 s and that was independent of extracellular Na(+), and a sustained current that was dependent on extracellular Na(+) and that was mediated by high-affinity GABA transporters. The receptor current was half-maximally activated at a GABA concentration of 32 microM, while the transporter current showed an affinity constant of 7.9 microM GABA. The receptor currents were blocked by bicuculline and picrotoxin and were also activated by muscimol or by other amino acids. The receptor currents are Cl(-) currents, as indicated by the close relationship between the reversal potential of these currents and the Cl(-) equilibrium potential. Using perforated-patch recordings, a mean intracellular Cl(-) concentration of 37 +/- 12 mM was determined in human Müller cells. Using electrophysiological and fluorescence imaging methods, it was revealed that GABA(A) receptors are unevenly distributed across the Müller cell membrane, with higher densities at the endfoot, at the soma, and at the distal sclerad end of the cells. It is concluded that GABA(A) receptor expression may allow a sensing of retinal GABAergic neuronal signal transmission by Müller cells.