Featured Research

from universities, journals, and other organizations

Channeling efforts to fight cystic fibrosis: Crosstalk between ion channels points to new therapeutic strategy

Date:
September 18, 2010
Source:
University of Pennsylvania School of Medicine
Summary:
Researchers have found a possible new target for fighting cystic fibrosis (CF) that could compensate for the lack of a functioning ion channel in affected CF-related cells.

Red shows the location of the protein NHE1 as a marker for the basolateral membranes, and the blue shows the location of the nuclei of the cells in the acinus.
Credit: Kevin Foskett, PhD; University of Pennsylvania School of Medicine

The lab of Kevin Foskett, PhD, the Isaac Ott Professor of Physiology at the University of Pennsylvania School of Medicine, has found a possible new target for fighting cystic fibrosis (CF) that could compensate for the lack of a functioning ion channel in affected CF-related cells.

Their finding appears in the Journal of Clinical Investigation.

The team explored the role of CFTR, the chloride ion channel mutated in CF patients, in fluid secretion by mucous gland cells. They used a recently developed transgenic pig model, in which the CFTR gene has been knocked out. The CFTR gene provides instructions for making a channel that transports negatively charged particles called chloride ions into and out of cells. The flow of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucous.

CF researchers had been held back because existing animal models did not fully mimic the problems seen in people with CF. In people, faulty mucous glands may contribute to airway dehydration and the problems associated with CF. Mucous glands found in the airways of the lung are important to breathing because they help clear inhaled irritants and bacteria. They are also the sites where important macromolecules critical for lung defense against pathogens are made.

CF is the most common genetic disease in the United States, affecting about 30,000 children and adults and about 70,000 worldwide. The CF mutation makes certain organs of the body susceptible to obstruction due to thick mucus secretions, especially in the lung where thick secretions lead to chronic infections. This requires a daily regimen of drugs and physical therapy to help clear airway secretions.

"We discovered, first, that the ion transport and signal transduction mechanisms in the pig cells appear to be precisely the same as those used in human cells, indicating that the pig is an excellent model for studies of human lung function and a valuable tool for elucidating pathology of lung disease in CF," notes Foskett.

The team also discovered that fluid secretion by the mucous cells -- in response to neurotransmitters -- requires CFTR. This secretion was absent in the pigs lacking CFTR. However, the same cells that lacked the CFTR chloride ion channel, mimicking the condition in human CF, expressed another, different chloride ion channel that could be activated by elevating intracellular calcium by the same neurotransmitters. The presence of both channels in the same mucous cells suggests that the calcium-activated chloride channel could be targeted therapeutically to compensate for lack of CFTR functioning channels in CF-harmed cells.

"This crosstalk between the signaling pathways that activate the two different chloride ion channels now gives us a completely new therapeutic strategy to think about," says Foskett. For example, the presence of the calcium-activated chloride channel would enable CF mucous cells to secrete in response to stimulation that would have normally required the CFTR channel. Drugs that could enhance the magnitude of the calcium response might also enable activation of calcium-activated chloride channel-mediated secretion in CF cells. Importantly, such agents might be able to lead to secretion only during times of physiological stimulus, utilizing the appropriate neural regulation of secretion that likely remains intact in CF.

This research was funded by the Cystic Fibrosis Foundation.


Story Source:

The above story is based on materials provided by University of Pennsylvania School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Robert J. Lee, J. Kevin Foskett. cAMP-activated Ca2+ signaling is required for CFTR-mediated serous cell fluid secretion in porcine and human airways. Journal of Clinical Investigation, 2010; 120 (9): 3137 DOI: 10.1172/JCI42992

Cite This Page:

University of Pennsylvania School of Medicine. "Channeling efforts to fight cystic fibrosis: Crosstalk between ion channels points to new therapeutic strategy." ScienceDaily. ScienceDaily, 18 September 2010. <www.sciencedaily.com/releases/2010/09/100917151848.htm>.
University of Pennsylvania School of Medicine. (2010, September 18). Channeling efforts to fight cystic fibrosis: Crosstalk between ion channels points to new therapeutic strategy. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2010/09/100917151848.htm
University of Pennsylvania School of Medicine. "Channeling efforts to fight cystic fibrosis: Crosstalk between ion channels points to new therapeutic strategy." ScienceDaily. www.sciencedaily.com/releases/2010/09/100917151848.htm (accessed July 28, 2014).

Share This




More Health & Medicine News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) 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:
from the past week

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