Modeling the Interactions Between Sodium Channels Provides Insight Into the Negative Dominance of Certain Channel Mutations.

Background: Na1.5 cardiac Na channel mutations can cause arrhythmogenic syndromes. Some of these mutations exert a dominant negative effect on wild-type channels.

Slowing of the Time Course of Acidification Decreases the Acid-Sensing Ion Channel 1a Current Amplitude and Modulates Action Potential Firing in Neurons.

Acid-sensing ion channels (ASICs) are H-activated neuronal Na channels. They are involved in fear behavior, learning, neurodegeneration after ischemic stroke and in pain sensation. ASIC activation has so far been studied only with fast pH changes, although the pH changes associated with many roles of ASICs are slow.

Distribution of cardiac sodium channels in clusters potentiates ephaptic interactions in the intercalated disc.

Key Points: It has been proposed that ephaptic conduction, relying on interactions between the sodium (Na ) current and the extracellular potential in intercalated discs, might contribute to cardiac conduction when gap junctional coupling is reduced, but this mechanism is still controversial. In intercalated discs, Na channels form clusters near gap junction plaques, but the functional significance of these clusters has never been evaluated. In HEK cells expressing cardiac Na channels, we show that restricting the extracellular space modulates the Na current, as predicted by corresponding simulations accounting for ephaptic effects.