Effects of nitric oxide on horizontal cells in the rabbit retina

Retinal horizontal cells display large receptive fields as a result of exte nsive electrical coupling via gap junctions. There is abundant evidence tha t these gap junctions are dynamically regulated by changes in the adaptatio nal state of the retina. The neuromodulator dopamine appears to play a majo r role in regulating gap junctional conductances of horizontal cells. Emerg ing evidence indicates that nitric oxide (NO) also acts as a neuromodulator in the retina and, more specifically, regulates the coupling between horiz ontal cells. In the present study, we examined the effects of a nitric oxid e, and its secondary messenger cGMP, on electrical and tracer coupling betw een A-type and between B-type horizontal cells in the rabbit retina. Applic ation of the NO donors S-nitroso-N-acetylpenicillamine (SNAP) or sodium nit roprusside (SNP) significantly reduced the coupling between horizontal cell s as evidenced by a decrease in their space constants, annulus-to-small spo t response ratios, and the extent of tracer coupling following injection wi th Neurobiotin. Further, application of SNP eliminated the increase in coup ling of horizontal cells normally seen with exposure to dim background illu mination. Application of 8-bromo-cGMP produced effects similar to those of the NO donors, consistent with the idea that the uncoupling actions of NO w ere mediated via a cGMP cascade. In addition, the NO donors and cGMP augmen ted the responsiveness of A- and B-type cells to both small and large spots of light. This augmentation appeared to be due to secondary effects on pho toreceptor transduction and/or photoreceptor-to-horizontal cell synaptic ef ficacy that were distinct from the actions on gap junctions. Our results su ggest that NO may mediate changes in coupling between horizontal cells rela ted to the adaptational state of the mammalian retina.