Piccoli Giuseppe, Del Pilar Gomez Maria, Nasi Enrico
Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118, USA.
J Physiol. 2002 Sep 1;543(Pt 2):481-94. doi: 10.1113/jphysiol.2002.022772.
The mechanisms by which Ca2+ regulates light adaptation in microvillar photoreceptors remain poorly understood. Protein kinase C (PKC) is a likely candidate, both because some sub-types are activated by Ca2+ and because of its association with the macromolecular 'light-transduction complex' in Drosophila. We investigated the possible role of PKC in the modulation of the light response in molluscan photoreceptors. Western blot analysis with isoform-specific antibodies revealed the presence of PKCalpha in retinal homogenates. Immunocytochemistry in isolated cell preparations confirmed PKCalpha localization in microvillar photoreceptors, preferentially confined to the light-sensing lobe. Light stimulation induced translocation of PKCalpha immunofluorescence to the photosensitive membrane, an effect that provides independent evidence for PKC activation by illumination; a similar outcome was observed after incubation with the phorbol ester PMA. Several chemically distinct activators of PKC, such as phorbol-12-myristate-13-acetate (PMA), (-)indolactam V and 1,2,-dioctanoyl-sn-glycerol (DOG) inhibited the light response of voltage-clamped microvillar photoreceptors, but were ineffective in ciliary photoreceptors, in which light does not activate the G(q)/PLC cascade, nor elevates intracellular Ca2+. Pharmacological inhibition of PKC antagonized the desensitization produced by adapting lights and also caused a small, but consistent enhancement of basal sensitivity. These results strongly support the involvement of PKC activation in the light-dependent regulation of response sensitivity. However, unlike adapting background light or elevation of [Ca2+]i, PKC activators did not speed up the photoresponse, nor did PKC inhibitors antagonize the accelerating effects of background adaptation, suggesting that modulation of photoresponse time course may involve a separate Ca2+-dependent signal.
钙离子调节微绒毛光感受器中光适应的机制仍知之甚少。蛋白激酶C(PKC)可能是一个候选因素,这既是因为某些亚型可被钙离子激活,也是因为它与果蝇中的大分子“光转导复合物”有关。我们研究了PKC在调节软体动物光感受器光反应中的可能作用。用亚型特异性抗体进行的蛋白质印迹分析显示视网膜匀浆中存在PKCα。分离细胞制剂中的免疫细胞化学证实PKCα定位于微绒毛光感受器中,优先局限于感光叶。光刺激诱导PKCα免疫荧光向感光膜转位,这一效应为光照激活PKC提供了独立证据;在用佛波酯PMA孵育后也观察到了类似结果。几种化学性质不同的PKC激活剂,如佛波醇-12-肉豆蔻酸酯-13-乙酸酯(PMA)、(-)吲哚拉辛V和1,2-二辛酰基-sn-甘油(DOG)抑制了电压钳制的微绒毛光感受器的光反应,但对睫状光感受器无效,在睫状光感受器中,光不会激活G(q)/PLC级联反应,也不会升高细胞内钙离子浓度。PKC的药理学抑制拮抗了适应光产生的脱敏作用,还导致基础敏感性有小幅但一致的增强。这些结果有力地支持了PKC激活参与光反应敏感性的光依赖性调节。然而,与适应背景光或细胞内钙离子浓度升高不同,PKC激活剂不会加快光反应,PKC抑制剂也不会拮抗背景适应的加速作用,这表明光反应时间进程的调节可能涉及一个独立的钙离子依赖性信号。