Stella S L, Thoreson W B
Department of Pharmacology and Department of Ophthalmology, University of Nebraska Medical Center, 985540 Nebraska Medical Center, Omaha, NE 68198-5540, USA.
Eur J Neurosci. 2000 Oct;12(10):3537-48. doi: 10.1046/j.1460-9568.2000.00235.x.
Synaptic transmission from vertebrate photoreceptors involves activation of L-type calcium currents (ICa). Dopamine is an important circadian neuromodulator in the retina and photoreceptors possess D2 dopamine receptors. We examined modulation of ICa by dopamine and cAMP in retinal slices and isolated cells of larval tiger salamander. Results show that dopamine and a D2 agonist, quinpirole, enhanced ICa in rods and red-, blue- and UV-sensitive small single cones but inhibited ICa 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 ICa in rods and small single cones, but inhibited ICa in large single cones. In contrast, forskolin and Sp-cAMPS, which stimulate PKA, inhibited ICa in rods and small single cones but enhanced ICa in large single cones. Sp-cAMPS also occluded effects of quinpirole. These results suggest that D2 receptors modulate ICa 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 ICa in large single cones and enhancement of rod ICa 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 ICa.
脊椎动物光感受器的突触传递涉及L型钙电流（ICa）的激活。多巴胺是视网膜中一种重要的昼夜节律神经调节剂，光感受器具有D2多巴胺受体。我们研究了多巴胺和环磷酸腺苷（cAMP）对虎螈幼体视网膜切片和分离细胞中ICa的调节作用。结果表明，多巴胺和D2激动剂喹吡罗增强了视杆细胞以及对红、蓝和紫外光敏感的小单锥细胞中的ICa，但抑制了对红光敏感的大单锥细胞中的ICa。D1激动剂SKF - 38393则没有作用。喹吡罗的作用可被百日咳毒素（PTx）预处理阻断；这表明PTx敏感的G蛋白参与其中。与多巴胺一样，Rp - cAMPS抑制cAMP依赖性蛋白激酶（PKA）可增强视杆细胞和小单锥细胞中的ICa，但抑制大单锥细胞中的ICa。相反，刺激PKA的福斯可林和Sp - cAMPS抑制视杆细胞和小单锥细胞中的ICa，但增强大单锥细胞中的ICa。Sp - cAMPS也消除了喹吡罗的作用。这些结果表明，D2受体通过抑制cAMP来调节ICa。光感受器对cAMP反应的差异与小单锥细胞和视杆细胞可能拥有与大单锥细胞不同的Ca2+通道亚型这一可能性相一致。多巴胺和喹吡罗对大单锥细胞中ICa的抑制以及对视杆细胞ICa的增强作用的结果出乎意料，因为先前的研究表明多巴胺会抑制视杆细胞输入并增强锥细胞向二级神经元的输入。因此，目前的结果表明，多巴胺能增强锥细胞输入并非源于光感受器ICa的调节。
