Congenital stationary night blindness is a hereditary condition that hampers a person’s ability to see in the dark. Scientists claim that this condition may be a result of the mutation in a calcium channel protein that transfers calcium in and out of cells. Ongoing research at John Hopkins University School of Medicine, is trying to understand this mutation further.
The team of researchers teased apart the molecular mechanism behind this mutation, thus discovering a generalized principle of how cells control calcium levels. This finding may also imply to other conditions inclusive of neurodegenerative diseases such as schizophrenia, Alzheimer’s, Parkinson’s and Huntington’s diseases.
David Yue, M.D., Ph.D., a professor of biomedical engineering and director of the Calcium Signals Lab at Hopkins explains that, “Calcium is so crucial for normal functions like heart contraction, insulin control and brain function. If calcium levels are off at any time, disease can ensue. Our new approach, watching calcium channels in action in living cells, allowed us to tease apart how they behave and how they’re controlled and find a new module that could be targeted for drug design.”
The peculiar calcium protein that seems to be the root cause of this type of night blindness, is missing the tail end of the protein. The team tested the ability of this protein in comparison with full-length versions, by checking on the maintenance of electrical current in cells. Normal channels indicate deteriorating current when the calcium levels are increased.
“We and others initially believed that the missing piece of the protein might behave to simply switch off the ability of elevated intracellular calcium to inhibit this current,” says Yue. “Without this module, there’s no way to down-regulate the calcium entering through these channels.”
However research indicates that the module functioned in a far better and different manner. Protein CaM apparently controls the calcium channels by sensing and binding to the calcium. CaM binds to the channels in such a manner that it stops their calcium transport function. In order to understand how the tail module in accordance with CaM controls the calcium channels, the scientists used a molecular optical sensor tool that allowed them to view live cells in different levels of CaM. With abundance of CaM, the sensor glowed cyan, while it glowed yellow when CaM was low.
It was indicated by research that the tail module does not simply switch off the channel sensitivity towards calcium, but rather the module neatly retunes the sensitivity of channels towards CaM and in turn how sensitive the transport function of channels is to intracellular calcium. In other words, the tail module adjusts the amount of calcium entering cells. Yue comments on the manner of adjustment by saying that it may bear on the many neurodegenerative diseases where calcium is dysregulated.
Following this research, the team is planning on investigating other types of live cells which include nerve and heart-cells. This is being done to check whether changes in calcium channel behavior may lead to disease-like states.
This research was published in the February 18 issue of Nature.