Am J Physiol Cell Physiol AJP: Regulatory, Integrative and Comparative Physiology
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Am J Physiol Cell Physiol (August 1, 2002). doi:10.1152/ajpcell.00216.2002
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Articles in PresS, published online ahead of print August 1, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00216.2002
Submitted on May 11, 2002
Accepted on July 26, 2002

Regulation of TonEBP transcriptional activator in MDCK cells following changes in ambient tonicity

Wolfgang Neuhofer1, Seung K Woo2, Ki Y Na2, Rita Grunbein1, Won K Park2, Ohnn Nahm2, Franz X Beck1, and Hyug M Kwon2*

1 Department of Physiology, University of Munich, Munich, Germany
2 Department of Medicine,, Johns Hopkins University, Baltimore, MD, USA

* To whom correspondence should be addressed. E-mail: mkwon{at}jhmi.edu.

In response to ambient hypertonicity, TonEBP stimulates certain genes including those encoding cytokines, transporters for organic solutes, and a molecular chaperone. TonEBP is regulated in a bi-directional manner- up-regulated by an increase in ambient tonicity while down-regulated by a decrease. To investigate the role of intracellular ionic strength in the activity of TonEBP, MDCK cells were subjected to a variety of conditions. Electron microprobe analysis was performed to measure intracellular electrolytes. Under conditions in which changes in cell volume were similar, TonEBP activity correlated with the intracellular ionic strength regardless of the external tonicity. On the other hand, inhibition of the Na, K-ATPase and high external K+ concentration led to a decreased activity of TonEBP despite a marked increase in the intracellular ionic strength. Since isotonic swelling is known to occur under these conditions, these data suggest that dilution of the cytoplasmic constituents inhibits the activity of TonEBP. We conclude that intracellular ionic strength and water content are major factors that determine the activity of TonEBP.




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