"When you get a spinal block or your dentist gives you a numbing injection, the local anesthetic drugs temporarily shut down sodium channels in the area of the procedure and prevent your brain from receiving the bad news from your nerves," Catterall said.
Over more than three decades, Catterall's lab and others at the UW have made many major discoveries about these tiny pores.
"But we had only a fuzzy, partial view of what the channels looked like," he said. "Now we have a much more detailed picture."
The ability to visualize the atomic structural details of the sodium channel was made possible by use of advanced methods of X-ray crystallography and data analysis in the laboratory of Ning Zheng, associate professor of pharmacology.
"A major problem in studying sodium channels is that they want to be in a cell membrane," Catterall said. New biochemical techniques allowed the research team to extract and purify bacterial sodium channels that they had expressed in the cell membranes of insect cells, and keep them in a stable, functional form for determination of their structure.
"Because of the importance of knowing the atomic structure of sodium channels, many labs have tried to work on it with no success," Zheng said. "We succeeded thanks to the collaborative approach we took and the right combination of talent, expertise, and resources." Payandeh, the first author of the paper, integrated expertise from both the Zheng and Catterall labs and his own past experience to tackle the challenge.
The structure emerged gradually over several months of laborious study.
"We all thought 'Eureka!' but nobody said it," Catterall said, recalling when he and his colleagues realized what they had accomplished.
Examining kinetic models of its intricate molecular structure will tell scie
|Contact: Leila Gray|
University of Washington