del Pilar Gomez Maria, Nasi Enrico
Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
J Neurosci. 2005 Feb 23;25(8):2042-9. doi: 10.1523/JNEUROSCI.5129-04.2005.
Calcium is thought to be essential for adaptation of sensory receptor cells. However, the transduction cascade of hyperpolarizing, ciliary photoreceptors of the scallop does not use IP3-mediated Ca release, and the light-sensitive conductance is not measurably permeable to Ca2+. Therefore, two typical mechanisms that couple the light response to [Ca]i changes seem to be lacking in these photoreceptors. Using fluorescent indicators, we determined that, unlike in their microvillar counterparts, photostimulation of ciliary cells under voltage clamp indeed evokes no detectable change in cytosolic Ca. Notwithstanding, these cells exhibit all of the hallmarks of light adaptation, including response range compression, sensitivity shift, and photoresponse acceleration. A possible mediator of Ca-independent sensory adaptation is cGMP, the second messenger that regulates the light-sensitive conductance; cGMP and 8-bromo cGMP not only activate light-dependent K channels but also reduce the amplitude of the light response to an extent greatly in excess of that expected from simple occlusion between light and chemical stimulation. In addition, these substances accelerate the time course of the photocurrent. Tests with pharmacological antagonists suggest that protein kinase G may be a downstream effector that controls, in part, the cGMP-triggered changes in photoresponse properties during light adaptation. However, additional messengers are likely to be implicated, especially in the regulation of response kinetics. These observations suggest a novel feedback inhibition pathway for signaling sensory adaptation.
钙被认为是感觉受体细胞适应过程所必需的。然而,扇贝的超极化纤毛光感受器的转导级联并不使用肌醇三磷酸(IP3)介导的钙释放,并且其光敏感电导对Ca2+的通透性无法测量。因此,这些光感受器似乎缺乏将光反应与胞内钙浓度([Ca]i)变化相耦合的两种典型机制。使用荧光指示剂,我们确定,与微绒毛光感受器不同,在电压钳制下对纤毛细胞进行光刺激确实不会引起胞质钙的可检测变化。尽管如此,这些细胞表现出光适应的所有特征,包括反应范围压缩、灵敏度变化和光反应加速。一种可能的不依赖钙的感觉适应介质是环鸟苷酸(cGMP),即调节光敏感电导的第二信使;cGMP和8-溴cGMP不仅能激活光依赖性钾通道,还能将光反应的幅度降低到远远超过光刺激和化学刺激之间简单叠加所预期的程度。此外,这些物质还能加速光电流的时间进程。药理学拮抗剂测试表明,蛋白激酶G可能是一种下游效应器,在一定程度上控制光适应过程中cGMP触发的光反应特性变化。然而,可能还涉及其他信使,尤其是在反应动力学的调节方面。这些观察结果提示了一种用于信号感觉适应的新型反馈抑制途径。