This is the readme.txt for the models associated with the paper
Huang CW, Huang CC, Wu SN. Activation by zonisamide, a newer anti-epileptic
drug, of large-conductance calcium-activated potassium channel in
differentiated hippocampal neuron-derived H19-7 cells. J Pharmacol Expt Ther
2006 [Epub ahead of print] (DOI:10.1124/jpet.106.116954).
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.
To run the models:
XPP: start with the command
This simulation will make graph similar to figure 8:
in the paper of Huang et al.
From Xi vs t, type ina or ikca to check sodium or calcium-activated potassium
Bard Ermentrout's website http://www.pitt.edu/~phase/
describes how to get and use xpp.
These model files were submitted by:
Drs. Sheng-Nan Wu and Chin-Wei Huang
National Cheng Kung University Medical Center
Tainan 70101, Taiwan