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)
Van den Berg
R J
RJ
Laboratory of Physiology, University of Leiden, The Netherlands.
Kok
P
P
Voskuyl
R A
RA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D002794:Choline / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D014635:Valproic Acid / Q000494:pharmacology*
D015221:Potassium Channels; D015222:Sodium Channels; D013779:Tetrodotoxin; D014635:Valproic Acid; D002794:Choline