Humans and Fish Share Common Protein for Smell

EMBARGOED UNTIL October 11, 2001Contact: Donna Krupa: 703.527.7357Cell: 703.967.2751 or [email protected]

Or Onsite APS Registration Desk in CanadaOctober 10-14, 2001Tel.: 1.403.762.6688

SPECIES AS DIVERSE AS HUMANS AND FISH SHARE COMMON PROTEIN FOR SMELL New research provides clues about possible defective regulation.

Banff, Alberta, Canada -- Olfactory marker protein (OMP) is a 19-kDa cytoplasmic protein selectively expressed in mature olfactory sensory neurons (OSNs) from fish to humans. OMP-null mice show delays in the onset and recovery phases of electro-olfactograms following odorant stimulation when compared to controls. As defective Ca2+ regulation could be responsible for these effects, Dr. Dan Schulze Department of Microbio-Immunology and Dr. Frank Margolis Department of Anatomy/Neurobiology and their colleagues at the University of Maryland examined the interaction of OMP and the Na+/Ca2+ exchanger in Xenopus oocytes and observed an OMP concentration-dependent decrease in Na+/Ca2+ exchanger activity. Their analyses provides the first molecular demonstration of the presence of Na+/Ca2+ exchangers in olfactory tissue and their interaction with OMP.

A more detailed discussion of these findings will be given by Dr. Schulze during the 4th International Conference on sodium-calcium exchange, Cellular and Molecular Physiology of Sodium-Calcium Exchange. The conference, a gathering of more than 100 international and inter-disciplinary experts, is being sponsored by the American Physiological Society (APS) on October 10-14, 2001 in Banff, Alberta, Canada.

Study Methodology and Findings Previous studies have demonstrated the involvement of Na+/Ca2+ exchange in OSN function, suggesting an interaction between OMP and Na+/Ca2+ exchangers. In this study, the researchers report that transcripts from three Na+/Ca2+ exchanger genes, NCX1, NCX2, NCX3, and three Na+/Ca2+K+ exchanger genes, NCKX1, NCKX2 and NCKX3, are expressed in rat and mouse olfactory tissues.

The research shows that the olfactory epithelium displays a distinct pattern of alternatively spliced isoforms for NCX1 different from that of the olfactory bulb. In addition, in olfactory epithelia the level of NCX1 mRNA is higher than those for NCX2 and NCX3. After olfactory bulbectomy, NCX1 mRNA in olfactory epithelia declines selectively, suggesting that NCX1 is expressed in OSNs.

To investigate the interaction of OMP and the Na+/Ca2+ exchanger, the researchers co-expressed one of the predominant NCX1 isoforms and OMP in Xenopus oocytes and observed an OMP concentration-dependent decrease in Na+/Ca2+ exchanger activity.

ConclusionTheir analyses provides the first molecular demonstration of the presence of Na+/Ca2+ exchangers in olfactory tissue and their interaction with OMP.

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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. Schulze, please contact Donna Krupa at 703.527.7357 (direct dial), 703.967.2751 (cell) or [email protected]. 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.