Mechanisms of Excitation and Adaptation in Limulus Photoreceptors

在美国东海岸发现的马蹄蟹，50多年来一直是研究视觉的模式生物。 自从Hartline的开创性工作，他获得了诺贝尔医学奖，很明显，这种生物的眼睛特别适合理解眼睛是如何工作的。 这项工作的目的是了解这些动物中的光敏神经元（光感受器）如何将光信号转化为可以传递给大脑的电响应（兴奋）。 这些动物兴奋的整个过程仍然不清楚，但很明显，这涉及到一系列反应。 许多研究人员进行了大量的研究，对最早的步骤有了清晰的了解，对最后一步，即电信号的实际产生，也有了一个强有力的开端。 中间步骤仍不清楚。 这项拨款将资助研究，以测试缺失的步骤是否是酶鸟苷酸环化酶的激活。 第二个目标是了解这些光感受器如何在背景光照变化时快速补偿，就像人们从昏暗的房间走到明亮的阳光下一样。这个过程被称为光适应。 虽然这一过程是由细胞内钙离子的释放启动的，但还不知道接下来会发生什么。 这项拨款将资助研究，以测试是否有任何几种蛋白激酶，一类酶，修改其他酶，行动，以引起光适应。 由于无脊椎动物的光转导基因可以使脊椎动物的神经元对光敏感，因此人们对这些问题的答案越来越感兴趣。 这一结果可能被开发成治疗失明或探测大脑功能。

The horseshoe crab found on the eastern seaboard of the United States has been a model organism for the study of vision for more than 50 years. Since the seminal work of Hartline, for which he got the Nobel Prize in Medicine, it has been clear that the eyes of this organism are particularly well suited for understand how the eye works. The proposed work has the aim of understanding how the light-sensitive neurons (photoreceptors) in these animals turn the light signal into an electrical response (excitation) that can be communicated to the brain. The overall process of excitation in these animals is still not understood, but it is clear that a long sequence of reactions is involved. A great deal of research by many investigators has led to a clear picture of the earliest steps and a strong beginning has been made towards an understanding of the last step, the actual generation of the electrical signal. The middle steps remain unclear. This grant will fund research to test whether the missing step is activation of the enzyme guanylate cyclase. A second goal is to understand how these photoreceptors rapidly compensate when background illumination changes, much as one would experience when going out into bright sunlight from a dim room. This process is termed light-adaptation. Although this process is known to be initiated by the release of calcium ions from stores inside the cell, it is not known what happens next. This grant will fund research to test whether any of several protein kinases, a class of enzymes that modify other enzymes, act to cause light adaptation. There has been increasing interest in understanding the answers to these questions because invertebrate phototransduction genes can be used to make vertebrate neurons sensitive to light. This result may be developed into a treatment for blindness or to probe brain function.