Goldfish cones contain CB1 receptors at the synaptic terminal,
selectively accumulate 3H-anandamide, and contain fatty acid
amide hydrolase-immunoreactivity, and voltage-gated calcium and potassium
currents are modulated by CB1 ligands (Yazulla et al.,
2000; Fan & Yazulla, 2003; Glaser et
al., 2005). These data suggest that a retinal mechanism may account for
some of the psychophysical effects of cannabis. Here, we studied the
effect of a cannabinoid agonist on cone light responses. Whole-cell
patch-clamp recordings were made from cones in the isolated goldfish
retina. Cones were stimulated with a spot of light of variable wavelength
and intensities in combination with voltage-and current-clamp protocols.
Pharmacological manipulation was performed using the cannabinoid agonist
WIN 55212-2 (10 μM). WIN had no effect on the absolute sensitivity of
the cones or on the kinetics of the onset response. However, the
light-offset response became faster, and the depolarizing overshoot was
enhanced. Time constant of the offset response was reduced from 292
± 28 ms to 180 ± 11 ms (n = 6) (P <
0.01) in the presence of WIN. Acceleration of the offset response was not
affected by flash length from 200 ms to 10 s. This was found under
current-clamp as well as under voltage-clamp conditions, indicating that
the effect of WIN was mediated directly or indirectly by modulation of the
cGMP-gated channels in the outer segment of the cones. The effects of WIN
were not blocked by the CB1 antagonist SR141716A. With a train of
“dark” flashes from a steady background, the photocurrent
recovered toward baseline more quickly with WIN than in Control. In
summary, cannabinoids speed up the dynamics of the phototransduction
deactivation cascade in the cone outer segments. The functional
consequence of this effect is to shorten the recovery time to the offset
of bright flashes, perhaps resulting in an increase in contrast
sensitivity.