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]