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The heart can only beat if electrically charged particles (ions) are transported back and forth across the plasma membrane of the heart cells. The sodium-potassium pump conducts this transport activity by pumping potassium ions into the cell interior and allowing sodium ions to flow out of the cell. Indirectly, it also regulates the concentration of calcium ions, which in turn control heartbeat. Patients with cardiac insufficiency receive drugs that affect the sodium pump in order to stabilize their heartbeat. Now, scientists at the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch have discovered a new function of the sodium pump. During embryonic heart morphogenesis, the pump generates a change in the ion concentration within and outside the cells (ion gradient). The scientists were able to demonstrate that the ion gradient determines the top (apical) and bottom (basal) of heart cell surfaces. Scientists call this cell polarity, a phenomenon vital for heart function. The sodium pump is also involved in cell junction maintenance, thus ensuring that the heart cells stay connected with one another. Without this sodium pump, the heart never develops. A report of the findings of PhD student Elena Cibrián-Uhalte and Dr. Salim Abdelilah-Seyfried (both MDC) and researchers of the University of California Los Angeles, USA has now been published in the Journal of Cell Biology (Jan. 15, 2007; 176, 2)*.
To date, cell biologists have identified a number of signal pathways which regulate organ development. "What is new and very surprising about this discovery is that ion gradients generated by the sodium pump regulate these fundamental cell biological processes, namely cell polarization and cell junction maintenance," said Dr. Seyfried, developmental biologist at MDC. He directs a laboratory that studies vertebrate development by using the zebrafish among other model systems. Zebrafish are only a few centimeters in length and their embryos are transparent, enabling researchers to observe each cell under the microscope.
Dr. Seyfried is especially interested in how epithelial cells on the outer and inner surfaces of the body polarize during organ development. This cell polarity is essential for organ functioning. "The most important finding of our present study is that the ion gradient regulates cell polarity," he said. "But we still need to find out exactly how ion gradients affect the polarization of myocardial cells during their early development. Moreover," he added, "for technical reasons, it is not possible for us to measure the ion concentrations in tiny (zebrafish) hearts that are only a few micrometers across."
The scientists in Berlin suspect that the defects in the sodium pump not only affect myocardial cell junction maintenance but also the development of the blood-brain barrier and the retina. If this hypothesis is confirmed, this means that the sodium pump plays a central role in the development of different types of epithelial cells not only in the heart but throughout the entire organism.
*Involvement of zebrafish Na+,K+ ATPase in myocardial cell junction maintenance
Elena Cibrián-Uhalte,1 Adam Langenbacher,2 Xiaodong Shu,2 Jau-Nian Chen,2,3,4,5 and Salim Abdelilah-Seyfried1,5
1Max Delbrück Center for Molecular Medicine, 3125 Berlin, Germany
2Department of Molecular, Cell, and Developmental Biology, 3Jonsson Comprehensive Cancer Center, and 4Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095
5 Corresponding authors salim@mdc-berlin.de or chenjn@mcdb.ucla.edu
Barbara Bachtler
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http://www.mdc-berlin.de/ueber_das_mdc/presse/index.htm
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