Pelucchi, Bruna and Aguiari, Gianluca and Pignatelli, Angela and Manzati, Elisa and Witzgall, Ralph and Senno, Laura del and Belluzzi, Ottorino (2006) Nonspecific Cation Current Associated with Native Polycystin-2 in HEK-293 Cells. Journal of the American Society of Nephrology - JASN 17 (2), pp. 388-397.
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Mutations in either PKD1 or PKD2 gene are associated with autosomal dominant polycystic kidney disease, the most common inherited kidney disorder. Polycystin-2 (PC2), the PKD2 gene product, and the related protein polycystin-L, function as Ca2+-permeable, nonselective cation channels in different expression systems. This work describes a nonspecific cation current (ICC) that is present in native HEK-293 cells and highly associated with a PC2-channel activity. The current is voltage dependent, activating for potentials that are positive to –50 mV and inactivating in a few milliseconds. It is sensitive to Cd2+, Gd3+, La3+, SKF96365, and amiloride. After silencing of PC2 by RNA interfering, cells show a reduced current that is restored by transfection with normal but not truncated PC2. Consistently, ICC is abolished by perfusion with an anti-PC2 antibody. Furthermore, heterologous expression of the PC1 cytoplasmic tail significantly increases ICC peak amplitude compared with native cells. This is the first characterization of such a current in HEK-293 cells, a widely used expression system for ion channels. These cells, therefore, could be regarded as a suitable and readily accessible tool to study interactions between native PC2/PC1 complex and other membrane proteins, thus contributing to the understanding of autosomal dominant polycystic kidney disease pathogenesis.
|Institutions:||Biology, Preclinical Medicine > Institut für Anatomie|
|Subjects:||500 Science > 570 Life sciences|
600 Technology > 610 Medical sciences Medicine
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Unknown|
|Deposited On:||02 Aug 2006|
|Last Modified:||25 Jul 2011 10:20|
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