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Science 13 February 1998:
Vol. 279. no. 5353, pp. 1027 - 1033
DOI: 10.1126/science.279.5353.1027
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Reports

Ca2+ Flux Through Promiscuous Cardiac Na+ Channels: Slip-Mode Conductance

L. F. Santana, * A. M. Gómez, *dagger W. J. Lederer ddagger

The tetrodotoxin-sensitive sodium ion (Na+) channel is opened by cellular depolarization and favors the passage of Na+ over other ions. Activation of the beta -adrenergic receptor or protein kinase A in rat heart cells transformed this Na+ channel into one that is promiscuous with respect to ion selectivity, permitting calcium ions (Ca2+) to permeate as readily as Na+. Similarly, nanomolar concentrations of cardiotonic steroids such as ouabain and digoxin switched the ion selectivity of the Na+ channel to this state of promiscuous permeability called slip-mode conductance. Slip-mode conductance of the Na+ channel can contribute significantly to local and global cardiac Ca2+ signaling and may be a general signaling mechanism in excitable cells.

Departments of Molecular Biology and Biophysics and Physiology, Medical Biotechnology Center and School of Medicine, University of Maryland, 725 West Lombard Street, Baltimore, MD 21201, USA.
*   These authors contributed equally to this paper.

dagger    Present address: INSERM U-390, CHU Arnaud de Villeneuve, Montpellier, France.

ddagger    To whom correspondence should be addressed. E-mail: jlederer{at}umaryland.edu

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