Voltage-gated sodium channel function from neonatal and adult rat cardiomyocytes was measured and compared. Channels from neonatal ventricles required an ∼10 mV greater depolarization for voltage-dependent gating events than did channels from neonatal atria and adult atria and ventricles. We questioned whether such gating shifts were due to developmental and/or chamber-dependent changes in channel-associated functional sialic acids. Thus, all gating characteristics for channels from neonatal atria and adult atria and ventricles shifted significantly to more depolarized potentials after removal of surface sialic acids. Desialylation of channels from neonatal ventricles did not affect channel gating. After removal of the complete surface N-glycosylation structures, gating of channels from neonatal atria and adult atria and ventricles shifted to depolarized potentials nearly identical to those measured for channels from neonatal ventricles. Gating of channels from neonatal ventricles were unaffected by such deglycosylation. Immunoblot gel shift analyses indicated that voltage-gated sodium channel α subunits from neonatal atria and adult atria and ventricles are more heavily sialylated than α subunits from neonatal ventricles. The data are consistent with approximately 15 more sialic acid residues attached to each α subunit from neonatal atria and adult atria and ventricles. The data indicate that differential sialylation of myocyte voltage-gated sodium channel α subunits is responsible for much of the developmental and chamber-specific remodeling of channel gating observed here. Further, cardiac excitability is likely impacted by these sialic acid–dependent gating effects, such as modulation of the rate of recovery from inactivation. A novel mechanism is described by which cardiac voltage-gated sodium channel gating and subsequently cardiac rhythms are modulated by changes in channel-associated sialic acids.
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1 March 2006
Article|
February 13 2006
Differential Sialylation Modulates Voltage-gated Na+ Channel Gating throughout the Developing Myocardium
Patrick J. Stocker,
Patrick J. Stocker
Department of Physiology and Biophysics and Program in Neuroscience, University of South Florida College of Medicine, Tampa, FL 33612
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Eric S. Bennett
Eric S. Bennett
Department of Physiology and Biophysics and Program in Neuroscience, University of South Florida College of Medicine, Tampa, FL 33612
Search for other works by this author on:
Patrick J. Stocker
Department of Physiology and Biophysics and Program in Neuroscience, University of South Florida College of Medicine, Tampa, FL 33612
Eric S. Bennett
Department of Physiology and Biophysics and Program in Neuroscience, University of South Florida College of Medicine, Tampa, FL 33612
Correspondence to Eric Bennett: [email protected]
Abbreviations used in this paper: CHO, Chinese hamster ovary; IVF, idiopathic ventricular fibrillation; LQTS, long QT syndrome; MLP, muscle LIM protein; SA, sialic acid.
Received:
October 05 2005
Accepted:
January 30 2006
Online ISSN: 1540-7748
Print ISSN: 0022-1295
The Rockefeller University Press
2006
J Gen Physiol (2006) 127 (3): 253–265.
Article history
Received:
October 05 2005
Accepted:
January 30 2006
Citation
Patrick J. Stocker, Eric S. Bennett; Differential Sialylation Modulates Voltage-gated Na+ Channel Gating throughout the Developing Myocardium . J Gen Physiol 1 March 2006; 127 (3): 253–265. doi: https://doi.org/10.1085/jgp.200509423
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