Valproate reduces excitability by blockage of sodium and potassium conductance. 1986

A M VanDongen, and M G VanErp, and R A Voskuyl

Effects of the antiepileptic drug valproate on sodium and potassium currents in the nodal membrane of peripheral nerve fibers of Xenopus laevis were determined by voltage- and current-clamp experiments. Under voltage-clamp conditions, a reduction of both sodium and potassium conductance (in a ratio of 2:1) was observed. Typically, 2.4 mM (400 mg/L) valproate reduced the sodium current 54% and the potassium current 26%, at a membrane potential of 5 mV. Valproate did not affect the leakage conductance. The reduction of potassium conductance was voltage dependent, being more pronounced at more positive membrane potentials. For the sodium system, a voltage dependency of the blockage could not be established. Under current-clamp conditions, valproate caused a reduction of excitability of nerve membrane: amplitude of the action potential and maximum rate of rise were decreased, whereas threshold potential was increased. The ability to follow high-frequency stimulation was impaired.

UI MeSH Term Description Entries
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D011188 Potassium An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D004827 Epilepsy A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313) Aura,Awakening Epilepsy,Seizure Disorder,Epilepsy, Cryptogenic,Auras,Cryptogenic Epilepsies,Cryptogenic Epilepsy,Epilepsies,Epilepsies, Cryptogenic,Epilepsy, Awakening,Seizure Disorders
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012964 Sodium A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. Sodium Ion Level,Sodium-23,Ion Level, Sodium,Level, Sodium Ion,Sodium 23
D014635 Valproic Acid A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS. Dipropyl Acetate,Divalproex,Sodium Valproate,2-Propylpentanoic Acid,Calcium Valproate,Convulsofin,Depakene,Depakine,Depakote,Divalproex Sodium,Ergenyl,Magnesium Valproate,Propylisopropylacetic Acid,Semisodium Valproate,Valproate,Valproate Calcium,Valproate Sodium,Valproic Acid, Sodium Salt (2:1),Vupral,2 Propylpentanoic Acid
D014981 Xenopus An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.

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