Navigation Links
Study provides insight on a common heart rhythm disorder
Date:10/7/2008

University of Iowa researchers and colleagues in France have identified a gene variant that causes a potentially fatal human heart rhythm disorder called sinus node disease. Also known as "sick sinus syndrome," the disease affects approximately one in 600 heart patients older than 65 and is responsible for 50 percent or more of the permanent pacemaker placements in the United States.

While the newly discovered gene variant is rare, the study provides insight into cellular mechanisms that regulate sinus node function and identifies an unanticipated new pathway for developing future therapies to regulate more common forms of sinus node disease. The findings, which also have research implications beyond heart disease, were published online Oct. 1 by the Proceedings of the National Academy of Sciences.

The team first analyzed data from two families in France: a family of 74 individuals, 26 of whom had sinus node dysfunction, and a family of 44 individuals, 13 of whom had the disease. Many of the affected individuals carried the same gene variant, and many experienced variable heart rate and bradycardia (dangerously low heart rate).

The investigators found that variants in a gene called ankyrin 2, or ANK2, resulted in dysfunction in the protein ankyrin-B in the members of these two different families, said the study's senior author Peter Mohler, Ph.D., associate professor of internal medicine in the University of Iowa Carver College of Medicine.

"While a small number of the patients displayed heart disease symptoms, including ventricular arrhythmias, the prevalence of sinus node dysfunction in these patients was extremely high. In fact, most required the implantation of cardiac pacemakers," said Mohler, who also is a Pew Scholar. "We predict that there are likely additional unidentified ankyrin variants in the larger general population that predispose humans to a combination of heart disease symptoms, including sinus node dysfunction, atrial fibrillation and ventricular arrhythmias.

"We were fortunate in this study to assemble an amazing collaboration between outstanding basic science laboratories at the University of Iowa and a group of internationally-renowned clinical electrophysiologists and geneticists in France," he added.

Blood circulation through the body depends on the coordinated contraction of specialized heart cells called ventricular cardiomyocytes. Cells in the sinoatrial node have a different role -- to maintain the heart's normal rhythm.

"There are thousands of ventricular cells in the heart, but there are only hundreds of sinoatrial node cells, so each nodal cell is absolutely critical for every beat of the human heart," Mohler said.

Because there are so few sinoatrial node cells, it has been difficult until recently for scientists to get sample cells from human or animal models, noted Thomas Hund, Ph.D., a member of the study team and University of Iowa associate in internal medicine.

"Building on others' discoveries, scientists in Professor Mohler's Professor Mark Anderson's, and Assistant Professor Long-Sheng Song's lab perfected methods to isolate mouse sinoatrial node cells. We were then able to image these cells and see what was different about them," Hund said.

Based on research previously published by Mohler in 2003 in the journal Nature, the investigators knew that in ventricular cardiomyocytes the protein ankyrin-B behaves like a "tugboat," delivering ion channels and anchoring them to specific domains on the cell membrane. These ion channels serve as conduits for the electrical activity that triggers cell contraction. The team found that ankyrin plays a similar critical role in organizing ion channels for the sinoatrial node cells, making it possible for these cells to maintain the normal heart rhythm.

"Taken together, these studies suggest that ankyrin-B and similar proteins organize cell systems to ensure that cellular components don't float around randomly," Mohler said. "Understanding how these cells behave may help us learn how to fix malfunctions that occur when people age or experience common forms of cardiac disease.

"Genes that make ankyrin or proteins like it are probably going to be the next set of genes targeted for understanding diseases that involve cells with electrical activity," he added. "In addition to heart disease, ankyrins could be involved in other 'excitable' cell diseases such as epilepsy, bipolar disease and diabetes."


'/>"/>

Contact: Becky Soglin
becky-soglin@uiowa.edu
319-335-6660
University of Iowa
Source:Eurekalert

Related biology news :

1. JDRF funded study links hygiene hypothesis to diabetes prevention
2. Study: Bird diversity lessens human exposure to West Nile Virus
3. Brookhaven scientists take off for southeastern Pacific climate study
4. Study finds genetic variant plays role in cleft lip
5. NASA picks ASU research team to guide study of search for life
6. NIH selects Case Western Reserve University to participate in National Childrens Study
7. Brown University and Women & Infants Hospital expand national childrens study to Bristol County
8. Study looks at psychological impact of gene test for breast cancer
9. UNC study on properties of carbon nanotubes, water could have wide-ranging implications
10. Sweat it out: UH study examines ability of sweat patches to monitor bone loss
11. Study reveals specific gene in adolescent men with delinquent peers
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/24/2016)... Ampronix facilitates superior patient care by providing unparalleled technology to leaders of the medical ... premium product recently added to the range of products distributed by Ampronix. ... ... ... Ampronix News ...
(Date:5/12/2016)... , May 12, 2016 WearablesResearch.com , ... published the overview results from the Q1 wave of ... recent wave was consumers, receptivity to a program where ... with a health insurance company. "We were ... share," says Michael LaColla , CEO of Troubadour ...
(Date:4/28/2016)... and BANGALORE, India , April 28, ... Systems, a product subsidiary of Infosys (NYSE: INFY ... announced a global partnership that will provide end ... use mobile banking and payment services.      (Logo: ... key innovation area for financial services, but it also plays ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... BEACH, Calif. , June 23, 2016  Blueprint ... new biological discoveries to the medical community, has closed ... co-founder Matthew Nunez . "We have ... us with the capital we need to meet our ... will essentially provide us the runway to complete validation ...
(Date:6/23/2016)... Francisco, CA (PRWEB) , ... June 23, 2016 ... ... (EDC) software, is exhibiting at the Pennsylvania Convention Center and will showcase its ... Annual conference. ClinCapture will also be presenting a scientific poster on Disrupting Clinical ...
(Date:6/23/2016)... , June 22, 2016  Amgen (NASDAQ: ... of the QB3@953 life sciences incubator to ... health. The shared laboratory space at QB3@953 was created ... a key obstacle for many early stage organizations - ... of the sponsorship, Amgen launched two "Amgen Golden Ticket" ...
(Date:6/22/2016)... DUBLIN , June 22, 2016 Research ... and Global Markets" report to their offering. ... $39.4 billion in 2014 from $29.3 billion in 2013. The market ... (CAGR) of 13.8% from 2015 to 2020, increasing from $50.6 billion ... and projected product forecasts during the forecast period (2015 to 2020) ...
Breaking Biology Technology: