Demonstrates a novel 'slip-mode conductance' in cardiac Na+ channels where beta-adrenergic activation or cardiotonic steroids allow Ca2+ permeation, contributing to cardiac Ca2+ signaling.
Hypothesis-generating for Ca2+ entry via Na+ channels; leaves open relevance to human HF or arrhythmias.
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.
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Santana et al. (1998) studied this question.
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