PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Johns Hopkins scientists identify a key to body's use of free calcium

2014-01-24
(Press-News.org) Contact information: Catherine Kolf
ckolf@jhmi.org
443-287-2251
Johns Hopkins Medicine
Johns Hopkins scientists identify a key to body's use of free calcium 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.

INFORMATION:

This work was supported by grants from the National Heart, Lung and Blood Institute (MERIT Award:5R37HL076795), the National Institute on Deafness and Other Communication Disorders (R01DC000276), the National Institute of General Medical Sciences (GM08752) and the National Institute of Mental Health (F31MH088109).

On the Web:

Link to article: http://dx.doi.org/10.1038/nchembio.1436

Yue Lab: http://www.bme.jhu.edu/people/primary.php?id=405

Media Contacts: Vanessa McMains; 410-502-9410; vmcmain1@jhmi.edu
Catherine Kolf; 443-287-2251; ckolf@jhmi.edu

END



ELSE PRESS RELEASES FROM THIS DATE:

Liars find it more rewarding to tell truth than fib when deceiving others

2014-01-24
TORONTO, ON – A University of Toronto report based on two neural imaging studies that monitored brain activity has found individuals are more satisfied to get a reward from telling the truth rather ...

Happy 10th anniversary Opportunity!

2014-01-24
PUBLIC RELEASE DATE: 23-Jan-2014 [ | E-mail ] var addthis_pub="eurekalert"; var addthis_options = "favorites, delicious, digg, facebook, twitter, google, newsvine, reddit, slashdot, stumbleupon, buzz, more" Share Contact: Diana Lutz dlutz@wustl.edu 314-935-5272 Washington University in St. Louis Happy 10th anniversary Opportunity! Whirlwind tour of the past 10 years of adventures and discoveries by mission scientist Ray Arvidson VIDEO: Ray Arvidson, deputy ...

CWRU study finds depression symptoms and emotional support impact PTSD treatment progress

2014-01-24
Many individuals with posttraumatic stress disorder (PTSD) also experience depression. Researchers at Case Western Reserve University found that during PTSD treatments, ...

Sports medicine physical of the future could help athletes 'ESCAPE' sudden cardiac death

2014-01-24
BOSTON (01/23/14)—A young athlete in seemingly excellent health dies suddenly from a previously ...

Are developing heart valves sensitive to environmental chemicals?

2014-01-24
Baltimore, MD—Exposure to environmental endocrine disrupters, such as bisphenol A, which mimic estrogen, is associated with adverse health effects. Bisphenol A is commonly found in plastic bottles ...

New clues may link hereditary cancer genes to increased risk of cancer from alcohol

2014-01-24
In laboratory experiments conducted on human cell lines at the Johns Hopkins Kimmel Cancer Center, scientists have shown that people carrying certain mutations in two hereditary ...

New computer model may aid personalized cancer care

2014-01-24
BOSTON – Dana-Farber Cancer Institute scientists have developed a mathematical model to predict how a patient's tumor is likely to behave and which of several possible treatments is most likely to be ...

Lab-grown, virus-free stem cells repair retinal tissue in mice

2014-01-24
Investigators at Johns Hopkins report they have developed human induced-pluripotent stem cells (iPSCs) capable of repairing damaged retinal vascular tissue in mice. The stem cells, derived from human ...

A scientific first: Physicists, physicians, engineers photograph radiation beams in the human body through the Cherenkov effect

2014-01-24
(Lebanon, NH 1/22/14) — A scientific breakthrough may give the field of radiation oncology new tools ...

Putting a brake on tumor spread

2014-01-24
A team of scientists, led by principal investigator David D. Schlaepfer, PhD, a professor in the Department of Reproductive Medicine at the University of California, San Diego School of Medicine, has found that a protein ...

LAST 30 PRESS RELEASES:

Study unexpectedly finds living in rural, rather than urban environments in first five years of life could be a risk factor for developing type 1 diabetes

Editorial urges deeper focus on heart-lung interactions in pulmonary vascular disease

Five University of Tennessee faculty receive Fulbright Awards

5 advances to protect water sources, availability

OU Scholar awarded Fulbright for Soviet cinema research

Brain might become target of new type 1 diabetes treatments

‘Shore Wars:’ New research aims to resolve coastal conflict between oysters and mangroves, aiding restoration efforts

Why do symptoms linger in some people after an infection? A conversation on post-acute infection syndromes

Study reveals hidden drivers of asthma flare-ups in children

Physicists decode mysterious membrane behavior

New insights about brain receptor may pave way for next-gen mental health drugs

Melanoma ‘sat-nav’ discovery could help curb metastasis

When immune commanders misfire: new insights into rheumatoid arthritis inflammation

SFU researchers develop a new tool that brings blender-like lighting control to any photograph

Pups in tow, Yellowstone-area wolves trek long distances to stay near prey

AI breakthrough unlocks 'new' materials to replace lithium-ion batteries

Making molecules make sense: A regional explanation method reveals structure–property relationships

Partisan hostility, not just policy, drives U.S. protests

The Journal of Nuclear Medicine Ahead-of-Print Tip Sheet: August 1, 2025

Young human blood serum factors show potential to rejuvenate skin through bone marrow

Large language models reshape the future of task planning

Narrower coverage of MS drugs tied to higher relapse risk

Researchers harness AI-powered protein design to enhance T-cell based immunotherapies

Smartphone engagement during school hours among US youths

Online reviews of health care facilities

MS may begin far earlier than previously thought

New AI tool learns to read medical images with far less data

Announcing XPRIZE Healthspan as Tier 5 Sponsor of ARDD 2025

Announcing Immortal Dragons as Tier 4 Sponsor of ARDD 2025

Reporting guideline for chatbot health advice studies

[Press-News.org] Johns Hopkins scientists identify a key to body's use of free calcium