A novel tetrodotoxin-insensitive, slow sodium current in striatal and hippocampal neurons

Slow inward currents modulate neuronal firing patterns and may generate depolarizing afterpotentials (DAPs). We report a novel, slow Na+ current (INaS) in striatal and hippocampal neurons that can generate DAPs. INaS activated at depolarizations greater than -40 mV, was tetrodotoxin insensitive, and activated and deactivated slowly over hundreds of milliseconds. INaS was dependent upon extracellular Na+, but was not affected by 0 mM extracellular Ca2+ or by Ca2+ channel blockers (Mn2+, Cd2+, or Co2+). A tetrodotoxin-insensitive, Na(+)-dependent plateau potential that was likely generated by INaS was shown to underlie DAPs during intracellular recordings from hippocampal CA1 pyramidal neurons. Membrane depolarizations and DAPs generated by INaS may contribute to alterations in neuronal firing and epileptiform bursting.