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.