Endogenous zinc as a retinal neuromodulator: evidence from the skate (Raja erinacea).

The effects of zinc on skate (Raja erinacea) bipolar cell responses to glutamatergic agonists were examined using whole-cell voltage-clamp recording. Isolated ON bipolar cell currents mediated by the metabotropic agonist trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (30 microM), L-2-amino-4-phosphonobutyrate (3-10 microM) and glutamate (0.3-10 microM) were blocked when zinc (1 microM) was added to the test solution. Similarly, isolated OFF bipolar cell responses to the ionotropic agonist kainate (300 microM) were blocked by zinc (1 microM). The effects of zinc were further studied using electroretinogram (ERG) recording. Skate eyecup preparations were superfused with picrotoxin (200 microM) to block GABAergic input. When histidine (100 microM), a zinc chelator, was added to the superfusate, ERG ON responses increased. This suggests that endogenous zinc plays a neuromodulatory role in the retina and is consistent with zinc's suppressive effect on isolated bipolar cells.