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M.L. Struik, S. Yazulla, M. Kamermans; Cannabinoids Modulate the Cone Light Response in Goldfish . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4168.
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Purpose: Psycophysical data show that cannabinoids enhance photosensitivity in human subjects. The expression of cannabinoid CB1 receptors in cones of rat, zebrafish and goldfish (Yazulla et al. 1999, 2000, 2001) suggests a retinal mechanism for this finding. To confirm this we studied the effect of cannabinoids on cone light responses and adaptation. Methods: Whole-cell patch clamp recordings were made of cones in the isolated goldfish retina. The cells were stimulated with a spot of light of variable wavelength and intensities in combination with voltage and current clamp protocols. Pharmacological manipulation was performed with bath application of the cannabinoid agonist WIN 55212-2 (10 µM), as well as modulation of the extracellular calcium concentration. Results: WIN did not affect the absolute sensitivity of the cones. It had, however, significant effects on the light offset response while leaving the onset response unaffected. The light offset response became faster and the overshoot was enhanced. 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 rather than by voltage-dependent currents. Nakatani & Yau (1988) reported previously that low extracellular calcium slowed down the response to light off in cones. This slowing down is due to inhibition of the calcium dependent light adaptation pathway. To study whether WIN affected the dynamics of this pathway, we lowered the extracellular calcium concentration. In this condition, the effects of WIN on the cone lightresponse were absent. Conclusions: Cannabinoids speed up the dynamics of the calcium-dependent dark adaptation pathway in cone outer segments. The functional consequence of this effect may be to shorten the recovery time to the offset of bright flashes and thereby cause an apparent increase in sensitivity.
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