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

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Science  13 Feb 1998:
Vol. 279, Issue 5353, pp. 1027-1033
DOI: 10.1126/science.279.5353.1027

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The tetrodotoxin-sensitive sodium ion (Na+) channel is opened by cellular depolarization and favors the passage of Na+ over other ions. Activation of the β-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.

  • * These authors contributed equally to this paper.

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

  • To whom correspondence should be addressed. E-mail: jlederer{at}

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