Differential modulation of rod and cone calcium currents in tiger salamander retina by D2 dopamine receptors and cAMP

Synaptic transmission from vertebrate photoreceptors involves activation of L-type calcium currents (I(Ca)). Dopamine is an important circadian neuromodulator in the retina and photoreceptors possess D2 dopamine receptors. We examined modulation of I(Ca) by dopamine and cAMP in retinal slices and isolated cells of larval tiger salamander. Results show that dopamine and a D2 agonist, quinpirole, enhanced I(Ca) in rods and red-, blue- and UV-sensitive small single cones but inhibited I(Ca) in red-sensitive large single cones. A D1 agonist, SKF-38393, was without effect. Quinpirole effects were blocked by pertussis toxin (PTx) pretreatment indicating involvement of PTx-sensitive G-proteins. Like dopamine, inhibition of cAMP-dependent protein kinase (PKA) by Rp-cAMPS enhanced I(Ca) in rods and small single cones, but inhibited I(Ca) in large single cones. In contrast, forskolin and Sp-cAMPS, which stimulate PKA, inhibited I(Ca) in rods and small single cones but enhanced I(Ca) in large single cones. Sp-cAMPS also occluded effects of quinpirole. These results suggest that D2 receptors modulate I(Ca) via inhibition of cAMP. Differences among the responses of photoreceptors to cAMP are consistent with the possibility that small single cones and rods may possess different Ca²⁺ channel subtypes than large single cones. The results with dopamine and quinpirole showing inhibition of I(Ca) in large single cones and enhancement of rod I(Ca) were unexpected because previous studies have shown that dopamine suppresses rod inputs and enhances cone inputs into second-order neurons. The present results therefore indicate that the dopaminergic enhancement of cone inputs does not arise from modulation of photoreceptor I(Ca).