Veratridine-enhanced persistent sodium current induces bursting in CA1 pyramidal neurons

Abstract

The mechanism of veratridine-induced bursting activity was studied in rat hippocampal CA1 pyramidal neurons. Veratridine (0.1-0.3 microM) induces bursting in previously normal pyramidal neurons. The current-voltage curves of untreated neurons show a slight deviation from the linear Ohmic relation; this deviation is known as the "depolarizing rectification". Veratridine markedly accentuates the depolarizing rectification so that a zero slope or negative slope appears in the current-voltage curve of these neurons. Both the veratridine-induced bursting activity and negative slope resistance are blocked by small concentrations of tetrodotoxin or by raising the calcium concentration of the superfusion medium. Under single-electrode voltage clamping, a subthreshold persistent (slowly inactivating) sodium current, which can be recorded in untreated neurons, is found to be enhanced in the veratridine-treated neurons. This current is thought to be responsible for the slow depolarizing phase of bursting activity and the development of negative slope resistance in the current-voltage relationship. The present results demonstrate that veratridine enhances the slowly inactivating sodium current, leading to the development of negative slope resistance and induction of bursting in rat hippocampal CA1 pyramidal neurons.