Effects of Topiramate on Sodium-Dependent Action-Potential Firing by Mouse Spinal Cord Neurons in Cell Culture
Article first published online: 2 AUG 2005
Volume 41, Issue Supplement s1, pages 21–24, January 2000
How to Cite
McLean, M. J., Bukhari, A. A. and Wamil, A. W. (2000), Effects of Topiramate on Sodium-Dependent Action-Potential Firing by Mouse Spinal Cord Neurons in Cell Culture. Epilepsia, 41: 21–24. doi: 10.1111/j.1528-1157.2000.tb02166.x
- Issue published online: 2 AUG 2005
- Article first published online: 2 AUG 2005
- Mechanism of action;
- Sodium channels;
- Antiepileptic drugs;
Purpose: The effects of topiramate (TPM) on sodium-dependent action potentials were studied by using cultured mouse spinal cord neurons.
Methods: The ability of TPM to limit (block) depolarization-induced spontaneous repetitive firing (SRF) was determined and compared with corresponding effects of phenytoin (PHT) and lamotrigine (LTG) in cultured mouse spinal neurons.
Results: Topiramate at concentrations of ges;3 μM caused a voltage-sensitive and time-dependent limitation of SRF that was associated with a decrease in the velocity of the upstroke of the action potential. At high concentrations (30–600 μM), TPM rapidly blocked SRF in about one third of the neurons tested and did not affect SRF in about one third. In some neurons, TPM caused an intermittent limitation (sputtering) of SRF (∼30% of the neurons) or blocked SRF only after a delay of several seconds (∼10%). This complex pattern of effects is distinctly different from that of PHT and LTG, in which the effect was always a rapid limitation or complete blockade of SRF. Another difference between TPM and the other anticonvulsants (AEDs) is that the effects of TPM were more dependent on the length of time the neurons were exposed to the compound and the intensity or duration of neuronal activity.
Conclusions: The results of this study do not support the concept that Na+ channel blockade is the primary mechanism responsible for the anticonvulsant activity of TPM.