Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Action Potentials
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Animals
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Calcium / metabolism*
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Cardiotonic Agents / pharmacology
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Cyclic AMP / metabolism
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Digoxin / pharmacology
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Enzyme Activation
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In Vitro Techniques
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Ion Channel Gating
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Isoproterenol / pharmacology
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Myocardial Contraction / physiology*
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Myocardium / cytology
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Myocardium / metabolism*
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Ouabain / pharmacology
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Patch-Clamp Techniques
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Rats
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Receptors, Adrenergic, beta / physiology
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Ryanodine Receptor Calcium Release Channel / metabolism
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Sarcoplasmic Reticulum / metabolism*
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Signal Transduction
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Sodium / metabolism
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Sodium Channel Blockers
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Sodium Channels / drug effects
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Sodium Channels / metabolism*
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Sodium-Calcium Exchanger / metabolism
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Tetrodotoxin / pharmacology
Substances
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Cardiotonic Agents
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Receptors, Adrenergic, beta
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Ryanodine Receptor Calcium Release Channel
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Sodium Channel Blockers
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Sodium Channels
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Sodium-Calcium Exchanger
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Tetrodotoxin
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Ouabain
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Digoxin
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Sodium
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Isoproterenol
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Calcium