Anomalous effect of permeant ion concentration on peak open probability of cardiac Na+ channels.
Human heart Na+ channels were expressed transiently in both mammalian cells and Xenopus oocytes, and Na+ currents measured using 150 mM intracellular Na+. Decreasing extracellular permeant ion concentration decreases outward Na+ current at positive voltages while increasing the driving force for the current. This anomalous effect of permeant ion concentration, especially obvious in a mutant (F1485Q) in which fast inactivation is partially abolished, is due to an alteration of open probability. The effect is only observed when a highly permeant cation (Na+, Li+, or hydrazinium) is substituted for a relatively impermeant cation (K+, Rb+, Cs+, N-methylglucamine, Tris, choline, or tetramethylammonium). With high concentrations of extracellular permeant cations, the peak open probability of Na+ channels increases with depolarization and then saturates at positive voltages. By contrast, with low concentrations of permeant ions, the open probability reaches a maximum at approximately 0 mV and then decreases with further depolarization. There is little effect of permeant ion concentration on activation kinetics at depolarized voltages. Furthermore, the lowered open probability caused by a brief depolarization to +60 mV recovers within 5 ms upon repolarization to -140 mV, indicative of a gating process with rapid kinetics. Tail currents at reduced temperatures reveal the rapid onset of this gating process during a large depolarization. A large depolarization may drive a permeant cation out of a site within the extracellular mouth of the pore, reducing the efficiency with which the channel opens.
Townsend
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C
Department of Physiology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Hartmann
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HA
Horn
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R
D000818:Animals; D002461:Cell Line, Transformed; D004594:Electrophysiology; D006801:Humans; D015640:Ion Channel Gating; D007477:Ions; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D009994:Osmolar Concentration; D010539:Permeability; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism* / Q000502:physiology; D014981:Xenopus
D007477:Ions; D015222:Sodium Channels; D012964:Sodium