Modulation by BNP of GABA receptors on ON-type rod bipolar cells is dependent on subcellular sites.

Brain natriuretic peptide (BNP) suppresses GABA(A) receptor-mediated current of ON-type rod-dominant bipolar cells (RBCs) in the rat retina. Here we report that such BNP-induced modulation is dependent on subcellular sites. Whole-cell currents could be induced by GABA focally applied to both dendrites/somata and axon terminals of isolated ON-type RBCs. Whilst the GABA currents induced at the axon terminal were significantly suppressed by BNP (50 nM), those at the dendrites/somata were hardly changed or slightly suppressed. Similar results were obtained when such experiments were performed in rat retinal slices. Calcium imaging showed that application of BNP (50 nM) caused a prominent increase in intracellular calcium concentrations (Ca(2+)) at the axon terminal, and the increase monotonically decayed when the acting site of BNP was moved away from the axon terminal along the cell: more distant, less significant. No detectable increase in Ca(2+) was found at the dendrites. Such increase in Ca(2+) could be completely blocked by pre-incubation with anantin, an antagonist of the NP-receptor-A (NPR-A). On the other hand, caffeine, an agonist of the ryanodine receptor, caused a similar subcellular site-dependent changes in Ca(2+), thus mimicking the BNP effect. All these results suggest that BNP-induced modulation of the activity of GABA receptors may be largely restricted to the inner retina.