Modulation of gap junctions between retinal neurons by intracellular messengers.

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Intracellular injection of cyclic GMP or soluble guanylate cyclase activators, such as nitric oxide (NO) and arachidonic acid, closed gap junctions between horizontal cells in carp (Cyprinus carpio) and turtle (Geoclemys reevesii) retinas. To determine whether the blocking effect of cyclic GMP on the gap junctions was through the action of cyclic GMP-dependent protein kinase, we examined the status of dye-coupling with Lucifer yellow CH among luminosity-type horizontal (H1) cells in the carp retina, by injection of protein kinase inhibitors into the cells. Dye-coupling among horizontal cells was observed after the intracellular injection of the mixture of cyclic GMP and a cyclic GMP-and cyclic AMP-dependent protein kinase, A-3 (N-(2-aminoethyl)-5-chloronaphthalene-1-sulfonamide hydrochloride). Dye-coupling was observed also after the injection of the mixture of cyclic GMP and cyclic GMP-dependent protein kinase inhibitor peptide (Arg-Lys-Arg-Ala-Arg-Lys-Glu) into the horizontal cell, indicating that the inhibitor suppressed the decoupling effect of cyclic GMP.The same kinase inhibitor did not suppress the decoupling effect of cyclic AMP on the gap junctions. On the other hand, a single cell was seen fluorescing after the injection of the mixture of cyclic GMP and cyclic AMP-dependent protein kinase inhibitor peptide (Arg-Gly-Try-Ala-Leu-Gly). These findings suggest that the blocking effct of cyclic GMP on gap-junctional intercellular communication among horizontal cells is through the action of cyclic GMP-dependent protein kinase, and that cyclic GMP modulates the gap junctions in a manner independent of the well-known dopamine/cyclic AMP pathway in the horizontal cell.