More MS news articles for Oct 2001

K-Dependent Na/Ca Exchangers in the Brain

Many aspects of the brain's function are critically dependent upon changes in the concentration of Ca2+ inside brain cells where the molecule plays several important signaling roles. Understanding these precisely fine-tuned changes will help scientists discover new ways to address stroke and neuro-degenerative diseases

http://www.newswise.com/articles/2001/10/BRAINAPS.PH2.html

12-Oct-01
American Physiological Society (APS)

Banff, Alberta, Canada -- Many aspects of the brain's function are critically dependent upon changes in the concentration of Ca2+ inside brain cells where the molecule plays several important signaling roles. For example, both the moment-to-moment communication between nerve cells as well as the molecular alterations that underlie memory and learning are dependent upon changes in Ca2+ concentration. Understanding these precisely fine-tuned changes will help scientists discover new ways to address stroke and neuro-degenerative diseases.

Jonathan Lytton, Ph.D., Professor, Department of Biochemistry and Molecular Biology at the University of Calgary, Calgary, Alberta, Canada and his research colleagues are pioneers in understanding certain types of sodium and calcium exchangers (NCX) in the brain. Dr. Lytton will discuss his work, focusing on the expression pattern and the functional properties of the K-dependent NCX isoforms in the brain during his presentation at the 4th International Conference, Cellular and Molecular Physiology of Sodium-Calcium Exchange. The conference, which Dr. Lytton will chair, is a gathering of more than 100 international and inter-disciplinary experts and being sponsored by the American Physiological Society (APS) on October 10-14, 2001 in Banff, Alberta, Canada.

Background

The concentration of Ca2+ in brain cells (as well as other cells) is regulated in space and time through the carefully orchestrated and coordinated action of many different protein molecules that transport Ca2+ across cellular membranes. It is only with a complete description of all Ca2+ transporting proteins, and the knowledge of how and where they work, that researchers will be able to understand cellular Ca2+ control fully. It is anticipated that such knowledge will provide novel potential therapeutic targets, and allow us to influence Ca2+ levels in predictable manners, so that treatments of disease and pathology associated with Ca2+ dys-regulation can begin.

In recent years, Dr. Lytton and his colleagues have discovered three new but unrelated genes whose products are expressed in brain at high levels. These gene products are transporters that move Ca2+ out of the cell across the outer membrane, relying upon Na+ and K+ ions to do so. Earlier research identified at least three other different types of transporters that can also move Ca2+ out of brain cells.

Using a combination of molecular biology, biochemistry and cell physiology, Lytton and his research team are currently investigating several members of the  potassium-dependent sodium-calcium exchanger gene family, focusing first on understanding where the different proteins are located in the brain, where they reside in individual brain cells and the details of how each molecule works. It is hoped that this effort may lead to the identification of potential new therapeutic targets.

Editor's Note: Background Information on Sodium-Calcium Exchange (NCX)

The physiological functions of vision, secretion and cardiac contractility are strongly dependent on sodium-calcium (Na+-Ca2+) exchange activity, according to the proceedings of the last NCX conference held in 1995 and published by the New York Academy of Sciences (Volume 779, p. xiii). Research efforts stem from the realization that "In many cell types, sodium-calcium exchange is the primary mechanism of calcium extrusion, and small changes of sodium-calcium exchange activity have large effects on cell function. In heart and in brain, sodium-calcium exchange activity likely becomes pivotal in pathological settings with possible outcomes of calcium overload, altered electrical activity and ultimately cell death." (p. xiii).

Since the Na+-Ca2+ exchanger (NCX) was first identified in heart muscle in 1968-1969 (p.7), it has been identified in virtually every tissue examined as well as in a variety of species, including human, dog, squid and fruitfly. The 1990 cloning of NCX1 from heart led to the discovery of different NCX isoforms in kidney, brain and vascular smooth muscle, as well as to the cloning of two new NCX genes, NCX2 and NCX3 from mammalian brain and skeletal muscle. A separate sub-family of Na+/Ca2+ exchangers, NCKX, was also identified in eye, brain and smooth muscle, that depend upon and transport potassium (K+) as well as Na+ and Ca2+. These data have provided further avenues for scientific exploration for the benefit of human health.

To set up an interview with Dr. Lytton, please contact Donna Krupa at 703.527.7357 (direct dial), 703.967.2751 (cell) or djkrupa1@aol.com. Or contact the APS registration desk on-site at 1.403.762.6688.

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.