HOFFPAUIR, B K*; GLEASON, E L; Louisiana State University; Louisiana State University: Nitric oxide modulates GABAergic signaling in retinal amacrine cells

Retinal amacrine cells are a diverse and relatively poorly understood group of interneurons that form synapses in the inner plexiform layer (IPL) of the vertebrate retina. The majority of these cells express GABA, a neurotransmitter traditionally considered to be inhibitory. In order to understand signaling in the inner retina, we must understand how GABAergic transmission is modulated in the IPL. This study focuses on the gaseous second messenger, nitric oxide (NO), and its role as a modulator of amacrine cell function. Immunohistochemical studies of the intact retina of the chicken reveal that a population of amacrine cells express the synthetic enzyme, brain nitric oxide synthase, suggesting that NO might play a role as a neuromodulator in the IPL. Whole cell voltage-clamp studies performed on amacrine cells in culture reveal that application of nitric oxide donors (SNAP, NOC 12, or NOC 18) enhances GABA-gated currents. Injecting a solution bubbled with NO into the perfusion line also enhances GABA-gated currents. This enhancement is due to a shift in the chloride reversal potential and in some cases, a change in conductance. Experiments using expired solutions fail to enhance the GABA-gated currents suggesting that the enhancement is a result of nitric oxide itself rather than nitric oxide reaction products accumulating in the test solutions. Under current-clamp conditions, application of the NO-containing solution converts the GABA response from hyperpolarizing to depolarizing. These results suggest that nitric oxide can convert inhibitory signals to excitatory signals at GABAergic amacrine cell synapses.