Evidence that different cation chloride cotransporters in retinal neurons allow opposite responses to GABA

GABA gating an anion channel primarily permeable to chloride can hyperpolar ize or depolarize, depending on whether the chloride equilibrium potential (E-Cl) is negative or positive, respectively, to the resting membrane poten tial (E-rest). If the transmembrane Cl- gradient is set by active transport , those neurons or neuronal regions that exhibit opposite responses to GABA should express different chloride transporters. To test this, we immunosta ined retina for the K-Cl cotransporter (KCC2) that normally extrudes chlori de and for the Na-K-Cl cotransporter (NKCC) that normally accumulates chlor ide. KCC2 was expressed wherever E-Cl is either known or predicted to be ne gative to E-rest (ganglion cells, bipolar axons, and OFF bipolar dendrites) , whereas NKCC was expressed wherever E-Cl is either known or predicted to be positive to E-rest (horizontal cells and ON bipolar dendrites). Thus, in the retina, the opposite effects of GABA on different cell types and on di fferent cellular regions are probably primarily determined by the different ial targeting of these two chloride transporters.