Find models by
Find models for
Find models of
Electrical synapses (gap junctions)
SenseLab mailing list
ModelDB related resources
Computational neuroscience ecosystem
Models in a git repository
Zonisamide-induced inhibition of the firing of APs in hippocampal neurons (Huang et al. 2007)
Download zip file
Help downloading and running models
Zonisamide (ZNS), a synthetic benzisoxazole derivative, has been used as an alternative choice in the treatment of epilepsy with a better efficacy and safety profile. However, little is known regarding the mechanism of ZNS actions on ion currents in neurons. We thus investigated its effect on ion currents in differentiated hippocampal 19-7 cells. The ZNS (30 uM) reversibly increased the amplitude of K+ outward currents and paxilline (1 uM) was effective in suppressing ZNS-induced increase of K+ outward currents. In inside-out configuration, ZNS (30 uM) applied to the intracellular face of the membrane did not alter single-channel conductance; however, it did enhance the activity of large-conductance Ca2+-activated K+ (BKCa) channels primarily by decreasing mean closed time. The EC50 value for ZNS-stimulated BKCa channels was 34 uM. This drug caused a left shift in the activation curve of BKCa channels with no change in the gating charge of these channels. ZNS at a concentration greater than 100 uM also reduced the amplitude of A-type K+ current in these cells. A simulation modeling based on hippocampal CA3 pyramidal neurons (Pinsky-Rinzel model) was also analyzed to investigate the inhibitory effect of ZNS on the firing of simulated action potentials. Taken together, this study suggests that in hippocampal neurons, during the exposure to ZNS, the ZNS-mediated effects on BKCa channels and IA could be one of the ionic mechanisms through which it affects neuronal excitability.
Huang CW, Huang CC, Wu SN (2007) Activation by zonisamide, a newer antiepileptic drug, of large-conductance calcium-activated potassium channel in differentiated hippocampal neuron-derived H19-7 cells.
J Pharmacol Exp Ther
(Click on a link to find other models with that property)
Neuron or other electrically excitable cell;
Hippocampus CA3 pyramidal GLU cell;
Ion Channel Kinetics;
Axonal Action Potentials;
Wu, Sheng-Nan [snwu at mail.ncku.edu.tw];
for information about:
Hippocampus CA3 pyramidal GLU cell
File not selected
<- Select file from this column.
Loading data, please wait...