Invited Symposium: Signal Transduction in Endothelium: Mechano-Sensing, Ion Channels and Intracellular Calcium
Lintschinger, B (Department of Pharmacology and Toxicology, Universität Graz, Austria)
Balzer, M (Department of Pharmacology and Toxicology, Universität Graz, Austria)
Endothelial cells respond to a variety of stimuli with activation of cation conductances that allow Na+ entry and membrane depolarization. Physiologic control of endothelial functions, e.g. via IP3-mediated release of Ca2+ from intracellular stores, as well as pathophysiologic dysfunction, e.g. in oxidative stress, are associated with activation of poorly selective cation channels. The molecular nature of these cation channels is still unclear. Recent evidence indicates that homologues of the Drosophila Trp protein may form cation channels in endothelial cells. This hypothesis was tested for human umbilical vein endothelial cells (HUVEC). RT-PCR experiments provided evidence for the expression hTrp1,3 and 4 in HUVEC. The role of Trp proteins in the IP3-induced cation conductance was tested by expression of an N-terminal fragment of hTrp3 (N-TRP) which exerts a dominant negative effect on Trp channel function. Intracellular administration of IP3 (100 µM) induced a substantial non-selective cation conductance in sham-transfected HUVEC. In contrast, HUVEC transfected with the dominant negative N-terminal fragment of hTrp3 failed to exhibit any non-selective cation currents upon challenge with IP3. Our results strongly suggest involvement of Trp proteins in non-selective cation conductances of vascular endothelial cells. The role of Trp channels in endothelial physiology and pathophysiology is discussed.
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|Groschner, K; Lintschinger, B; Balzer, M; (1998). Role of Non-selective Cation Channels in Endothelial Physiology and Pathophysiology. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/nilius/groschner0331/index.html|
|© 1998 Author(s) Hold Copyright|