Ca 2+ Flux Through Promiscuous Cardiac Na + Channels: Slip-Mode Conductance

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 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 (Ca ²⁺ ) 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 Ca ²⁺ signaling and may be a general signaling mechanism in excitable cells.