Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 31 July 2001
Vol. 2001, Issue 93, p. tw1
[DOI: 10.1126/stke.2001.93.tw1]

EDITORS' CHOICE

Channels Lethally Unglycosylated

Cardiac arrhythmias are often fatal in patients with heart failure. Ufret-Vincenty et al. studied mechanisms underlying arrhythmias in a mouse model of heart failure, the MLP–/– mouse in which the gene encoding the cardiac LIM domain protein is disrupted. Myocytes from MLP–/– mice showed prolonged action potentials, which resulted in lengthening of the QT interval on electrocardiograms, a phenomenon like long QT syndrome in humans. Alterations in the Na+ current (INa) were the likely cause of the action potential prolongation and increase in arrhythmogenic voltage fluctuations, called early after-depolarizations. Analysis of the Na+ channel α subunit by Western blotting suggested that along with an overall decrease in abundance in MLP–/– myocytes, the α subunit exhibited altered glycosylation. Treatment of wild-type mouse myocytes with neuramidase to cleave sialic acid reproduced the altered INa characteristics observed in the MLP–/– myocytes. Thus, altered glycosylation of cardiac Na+ channels in heart failure patients may represent a mechanism for the production of fatal arrhythmias.

C. A. Ufret-Vincenty, D. J. Baro, W. J. Lederer, H. W. Rockman, L. E. Quiñones, L. F. Santana, Role of sodium channel deglycosylation in the genesis of cardiac arrhythmias in heart failure. J. Biol. Chem. 276, 28197-28203 (2001). [Abstract] [Full Text]

Citation: Lethally Unglycosylated. Sci. STKE 2001, tw1 (2001).


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882