Valproate and sodium currents in cultured hippocampal neurons

Cultured rat hippocampal neurons with short processes were investigated using the whole cell voltage clamp under conditions appropriate for isolating Na+ currents. After incubation of the neuron culture for a period of 15-30 min in 1 mM sodium valproate, several parameters of the Na+ current were changed. The peak Na+ conductance gp, measured using hyperpolarizing prepulses, was reduced by valproate in a voltage-dependent manner. In the membrane voltage range from -30 to +20 mV, this reduction showed a linear dependence on voltage, increasing from about zero to approximately 30% of gp, the maximum peak Na+ conductance of the neuron. At the holding voltage of -70 mV, the inactivation parameter h infinity decreased from 0.88 in the control to 0.64 in the valproate solution. This reduction originated mainly from a 10 mV shift in the sigmoid relation between h infinity and membrane voltage along the voltage axis to hyperpolarizing potentials. The decay of the maximum peak Na+ current (inactivation) could be fitted by a biexponential function. Time constants of the fast and slow component at -20 mV decreased in valproate by about 50%. Valproate also retarded the recovery from inactivation, as determined at the holding voltage. The sigmoid recovery from inactivation could reasonably be described by an exponential function with time constant tau r and delay time delta t. Both tau r and delta t increased more than 200% in valproate. Our results indicate that valproate affected the Na+ current in hippocampal neurons in a way that contributed to a considerable depression of Na+ reactivation.(ABSTRACT TRUNCATED AT 250 WORDS)