Therapeutic concentrations of valproic acid inhibit fast TTX-sensitive voltage-gated sodium channels in prefrontal cortex pyramidal neurons

• Autorzy: Szulczyk B.
• Języki publikacji: EN

Abstrakty

EN

Valproic acid is a widely used antiepileptic and mood‑stabilizing drug. Its mechanism of action has not been fully elucidated. The aim of this study was to test the effect of different therapeutic concen‑ trations of valproic acid on fast TTX‑sensitive volt‑ age‑gated sodium channels. These channels play a very important role in neuronal physiology and in epileptic activity. Voltage‑gated sodium currents were recorded using the voltage‑clamp technique. Dispersed prefrontal cortical pyramidal neurons were tested. At a –90 mV holding potential, valpro‑ ic acid (200 μM) slightly inhibited the maximal am‑ plitude of sodium channels. The effect of the drug on the maximal amplitude of sodium currents was much more pronounced when a –50 mV depolarized holding potential was applied. At this holding po‑ tential, three doses were tested: 200 µM, 2 µM and 0,02 µM. Valproic acid did not influence activation but shifted the inactivation curve of fast voltage‑gat‑ ed sodium channels towards hyperpolarization. This means that the sodium channels were inhibited by valproate over the range of membrane potentials. Recovery from inactivation was the same in the con‑ trol and in the presence of valproic acid. Use‑de‑ pendent blockade was tested at 10 Hz and 50 Hz. In every condition, valproic acid did not influence the use‑dependent blockade. The main finding of this study is that therapeutic concentrations of valproic acid inhibit fast voltage‑gated TTX‑sensitive sodium currents when they are evoked from a depolarized holding potential. Thus, fast voltage‑gated sodium channels contribute to the pharmacological effect of valproate.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2018
• Tom: 78
• Numer: Suppl.1
• Opis fizyczny: p.8

Twórcy

autor

Szulczyk B.

• Department of Drug Technology and Pharmaceutical Biotechnology, The Medical University of Warsaw, Warsaw, Poland
• Department of Physiology and Pathophysiology, The Medical University of Warsaw, Warsaw, Poland