Ionotropic non-N-methyl-D-aspartate agonists induce retraction of dendritic spinules from retinal horizontal cells.

Horizontal cells invaginate the photoreceptors in the retina and form reciprocal synaptic connections in the cone pedicles. In fish retina the pattern of synaptic connections is plastic and modulated by the ambient light conditions. Numerous dendritic spinules protrude from the terminal horizontal-cell dendrites into the cone pedicle when the retina is light-adapted and are retracted during dark adaptation. The retraction of spinules can be induced during maintained illumination by an injection of the putative cone transmitter L-glutamate or its analogue kainic acid into the vitreous humor. The formation and the retraction of spinules have a time course of minutes. Activation of protein kinase C through phorbol esters initiates the formation of spinules, but the retraction has not yet been linked to a specific second messenger. Herein we report that physiological concentrations of the glutamate analogs quisqualic acid and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid induce retraction of spinules during maintained illumination. (+/-)-trans-1-Amino-1,3-cyclopentanedicarboxylic acid, an agonist for the metabotropic quisqualic acid receptor, was without effect on spinule retraction. N-Methyl-D-aspartate and L-2-amino-4-phosphonobutyric acid, agonists at other types of glutamate receptors, were also without any effect. The effects of the active agonists persisted when synaptic transmission was blocked. In the presence of the ionotropic quisqualate receptor antagonist 6-cyclo-7-nitro-quinoxaline-2,3-dione the effects of all active agonists were blocked. These results demonstrate that activation of ionotropic quisqualate receptors on the horizontal-cell membrane can induce dendritic spinule retraction, a process associated with dark adaptation.