Role of membrane potential in the regulation of endothelial cell deformability

• Applicant: Professor Dr. Hans Oberleithner
• Subject Area: Anatomy and Physiology
• Term: from 2008 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 53759782

There is accumulating evidence that blood vessels are targets for aldosterone. Recent data indicate that, under certain circumstances, the steroid renders endothelia stiff and vulnerable. Although the clinical relevance is obvious and aldosterone antagonists are successfully used for treatment, the mechanism of aldosterone action in endothelial cells is unknown. The electrical plasma membrane potential difference, dominated by the activities of various ion channels, could play a key role in the regulation of endothelial stiffness and in the control of the cell's deformability. Aldosterone leads to the expression of epithelial sodium channels in the apical membrane of endothelial cells which is supposed to depolarize the cells. To test the role of the membrane potential and the underlying ion channel activities we designed a project to manipulate and measure the membrane potential difference of endothelial cells applying fluorescence methods. In parallel, cell stiffness and deformability (by using the atomic force microscope as a nanosensor) will be quantified. Finally, nitric oxide formation will be related to membrane potential and cell stiffness. The working hypothesis is that the magnitude of the endothelial cell membrane potential difference determines the cell's deformability and, as a consequence, determines NO release and vascular smooth muscle tone. By using blockers and agonists we will functionally identify the different ion channels underlying the endothelial membrane potential difference with emphasis on aldosteroneregulated epithelial sodium channels. The aim of this project is to identify the key players of the membrane-born mechanisms that cause the changes in cellular deformability and to relate them to the physiological functions of the endothelium.

• DFG Programme: Research Grants
• Major Instrumentation: AFM Multimode V head stage for cell stiffness measurements
• Instrumentation Group: 5091 Rasterkraft-Mikroskope