Cannabinoid CB1 receptors are distributed
throughout the CNS and interact with GABA, glutamate, and
dopamine systems. Cannabinoids have effects on the visual
system, some of which may have a retinal component, particularly
the enhancement of photosensitivity. We used immunocytochemistry
and whole-cell recording to study cannabinoids in the goldfish
retina. Immunoblots of an antiserum against amino acids
(1-14) of the rat CB1 receptor produced a single
band in goldfish retina at about 70 kDa. Light microscope
immunocytochemistry of CB1 receptor immunoreactivity
(CB1R-IR) revealed intense staining of Müller
cells and weaker staining of ON bipolar cells (verified
with double labeling with PKC-IR) and the outer and inner
plexiform layers. Ultrastructural analysis revealed that
CB1R-IR was localized intracellularly as well
as on the plasma membrane of photoreceptor terminals, bipolar
cell terminals and, rarely, amacrine cell boutons. Membrane-associated
CB1R-IR was restricted to cone pedicles at sites
removed from the synaptic ribbon. Regarding bipolar cells,
membrane-associated CB1R-IR was found at 93%
of the synaptic terminals in sublamina b (ON-type)
and only at 33% of the synaptic terminals in sublamina
a (OFF-type). Whole-cell recordings from large
ON-type Mb bipolar cells showed that the delayed rectifier
(IK(V)) was rapidly and reversibly
inhibited by 1 μM of the cannabinoid agonists CP 54490
and (+)-WIN 55212-2, effects blocked completely by the antagonist
SR 141716A (1 μM). Inhibition of IK(V)
in the Mb bipolar cells by cannabinoids should result in a more
tonic ON response to increments of light. As such, cannabinoids
may play a role in modulating the temporal aspects of signaling
in the retina.