Featured Research

from universities, journals, and other organizations

Scientists identify key to body's use of free calcium

Date:
January 23, 2014
Source:
Johns Hopkins Medicine
Summary:
Scientists report they have figured out a key step in how "free" calcium -- the kind not contained in bones -- is managed in the body, a finding that could aid in the development of new treatments for a variety of neurological disorders that include Parkinson's disease.

Scientists at Johns Hopkins report they have figured out a key step in how "free" calcium -- the kind not contained in bones -- is managed in the body, a finding that could aid in the development of new treatments for a variety of neurological disorders that include Parkinson's disease.

Appearing online this week in Nature Chemical Biology, the researchers describe their use of tiny "lights" and chemical "leashes" to unveil how calcium is controlled.

Electrical signals carried by free-floating calcium ions are "wildly important to keeping the second-by-second functions of the body going," says David Yue, M.D., Ph.D., professor of biomedical engineering and neuroscience at The Johns Hopkins University.

Yue, who led the research team of graduate students Philemon Yang and Manu Ben Johny, explains that large proteins called calcium channels are the gatekeepers that determine when calcium enters cells. Embedded in cell membranes, these channels open and shut to regulate calcium flow into the cell. When calcium goes into cells, it sets off a cascade of vital activity, but just the right amount of calcium must enter -- otherwise, problems arise.

To achieve this balance, two chemical regulators bind to calcium channels as a brake and accelerator for calcium entry. Calmodulin, one type of calcium channel-binding protein, stops calcium from flowing through, while other proteins, known as calcium- Yue, who led the research team of graduate students Philemon Yang and Manu Ben Johny, explains that large proteins called calcium channels are the gatekeepers that determine when calcium enters cells.

Embedded in cell membranes, these channels open and shut to regulate calcium flow into the cell. When calcium goes into cells, it sets off a cascade of vital activity, but just the right amount of calcium must enter -- otherwise, problems arise. To achieve this balance, two chemical regulators bind to calcium channels as a brake and accelerator for calcium entry. Calmodulin, one type of calcium channel-binding protein, stops calcium from flowing through, while other proteins, known as calcium-binding proteins, accelerate calcium entry.

In their research, Yue and his colleagues examined specific calcium channels embedded in the membranes of nerve cells in the brain to see how calmodulin and CaBP4, a particular calcium-binding protein, latch onto the channels.

They rigged the odds in favor of calmodulin binding by genetically engineering calcium channels that were tethered to calmodulin by a short, flexible strand of amino acids. But to their surprise, Yue says, calcium-binding proteins stuck to the calcium channels at the same time, suggesting that each regulator has its own parking space on the channel, whereas previous theories suggested a single space.

To further examine the relationships among these regulators of calcium, the scientists used markers that glow in different colors and attached them to calcium channels, calmodulin and CaBP4. When two molecules locked together, the color changed. By measuring color changes, the researchers could then tell which molecules bound to each other.

In their research, Yue and his colleagues examined specific calcium channels embedded in the membranes of nerve cells in the brain to see how calmodulin and CaBP4, a particular calcium-binding protein, latch onto the channels.

They rigged the odds in favor of calmodulin binding by genetically engineering calcium channels that were tethered to calmodulin by a short, flexible strand of amino acids. But to their surprise, Yue says, calcium-binding proteins stuck to the calcium channels at the same time, suggesting that each regulator has its own parking space on the channel, whereas previous theories suggested a single space.

To further examine the relationships among these regulators of calcium, the scientists used markers that glow in different colors and attached them to calcium channels, calmodulin and CaBP4. When two molecules locked together, the color changed. By measuring color changes, the researchers could then tell which molecules bound to each other.

"Our experiments established that calmodulin and calcium-binding proteins work by binding to distinct parts of the calcium channel," Yue says. "More generally, we have been able to investigate how large molecules such as these function in living cells."

The "live light show" permitted by the use of light markers should help scientists develop new drugs that target calcium channels, Yue adds. Some such drugs already exist, including calcium channel blockers that lower blood pressure by targeting a particular kind of calcium channel found in blood vessels.

Blocking calcium channels might help with other diseases, too, Yue says. For example, researchers have found that an overload of calcium in certain parts of the brain may drive some neurodegenerative diseases, such as Parkinson's. Blocking the calcium channels found in those trouble spots -- the kind of calcium channels in Yue's study -- could be a way to fight the debilitating brain disease.


Story Source:

The above story is based on materials provided by Johns Hopkins Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Philemon S Yang, Manu Ben Johny, David T Yue. Allostery in Ca2 channel modulation by calcium-binding proteins. Nature Chemical Biology, 2014; DOI: 10.1038/nchembio.1436

Cite This Page:

Johns Hopkins Medicine. "Scientists identify key to body's use of free calcium." ScienceDaily. ScienceDaily, 23 January 2014. <www.sciencedaily.com/releases/2014/01/140123142043.htm>.
Johns Hopkins Medicine. (2014, January 23). Scientists identify key to body's use of free calcium. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2014/01/140123142043.htm
Johns Hopkins Medicine. "Scientists identify key to body's use of free calcium." ScienceDaily. www.sciencedaily.com/releases/2014/01/140123142043.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How Nigeria Beat Its Ebola Outbreak

How Nigeria Beat Its Ebola Outbreak

Newsy (Oct. 20, 2014) The World Health Organization has declared Nigeria free of Ebola. Health experts credit a bit of luck and the government's initial response. Video provided by Newsy
Powered by NewsLook.com
Another Study Suggests Viagra Is Good For The Heart

Another Study Suggests Viagra Is Good For The Heart

Newsy (Oct. 20, 2014) An ingredient in erectile-dysfunction medications such as Viagra could improve heart function. Perhaps not surprising, given Viagra's history. Video provided by Newsy
Powered by NewsLook.com
Ebola Worries End for Dozens on U.S. Watch Lists

Ebola Worries End for Dozens on U.S. Watch Lists

Reuters - US Online Video (Oct. 20, 2014) Forty-three people who had contact with Thomas Eric Duncan, the first person diagnosed with Ebola in the U.S., were cleared overnight of twice-daily monitoring after 21 days of showing no symptoms. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Fauci: Ebola Protocols to Focus on Training

Fauci: Ebola Protocols to Focus on Training

AP (Oct. 20, 2014) Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, says he expects revised CDC protocols on Ebola to focus on training, observation and ensuring health care workers are more protected. (Oct. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins