diff --git a/README.md b/README.md new file mode 100644 index 0000000..88f5a2d --- /dev/null +++ b/README.md @@ -0,0 +1,64 @@ +This is the readme.txt for the models associated with the paper. + +Huang CW, Tsai JJ, Huang CC, Wu SN. Experimental and simulation +studies on the mechanisms of levetiracetam-mediated inhibition of +delayed-rectifier potassium current (KV3.1): contribution to the +firing of action potentials. *J Physiol Pharmacol* (2009) in press. + +Levetiracetam (LEV) is an S-enantiomer pyrrolidone derivative with +established antiepileptic efficacy in generalized epilepsy and partial +epilepsy. However, its effects on ion currents and membrane potential +remain largely unclear. In this study, we investigated the effect of +LEV on differentiated NG108-15 neurons. In these cells treated with +dibutyryl cyclic AMP, the expression level of the KV3.1 mRNA was +elevated. With the aid of patch clamp technology, we found that LEV +was able to suppress the amplitude of delayed rectifier K+ current +(IK(DR)) in a concentration-dependent manner with an IC50 value of 37 +uM in differentiated NG108-15 neurons. LEV (30 uM) shifted the +steady-state activation of IK(DR) to a more positive potential by 10 +mV, without shifting the steady-state inactivation of IK(DR). Neither +Na+, nor erg (ether-a-go-go -related)-mediated K+ and ATP-sensitive K+ +currents were affected by LEV (100 uM). LEV increased the duration of +action potentials in current clamp configuration. Simulation studies +in a modified Hodgkin-Huxley neuron and network unraveled that the +reduction of slowly inactivating IK(DR) resulted in membrane +depolarization accompanied by termination of the firing of action +potentials in a stochastic manner. Therefore, the inhibitory effects +on slowly inactivating IK(DR) (Kv3.1-encoded current) may constitute +one of the underlying mechanisms through which LEV affects neuronal +activity in vivo. + +## To run the models: + +XPP: start with the command +`xppaut hh200x50-LEV01.ode` +(or similar) + +This simulation will make graphs similar to figure 10A in the paper of +Huang et al. + +From Viewaxes, select Array, then assign to: column 1: VE0, Ncols: +200, Row 1: 10, NRows: 200, Rowskip:10, Zmin: -90, Zmax: 40 + +Back at the main menu select "Xi vs t", then change VE0 to VE4, +finally select Initialconds -> Go to generate the following graphs: + +![screenshot 2](./Figure10a02.JPG) +![screenshot 1](./Figure10a01.JPG) + +When gk3 was changed to 4 and eta to 10, graphs will be similar to +Figure 10B. + +Bard Ermentrout's website [http://www.pitt.edu/~phase/](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 College +Tainan 70101, Taiwan +snwu@mail.ncku.edu.tw + +--- + +2025-06-02: Converted README to Markdown. \ No newline at end of file diff --git a/readme.html b/readme.html deleted file mode 100644 index 508968f..0000000 --- a/readme.html +++ /dev/null @@ -1,62 +0,0 @@ -
-This is the readme.txt for the models associated with the paper.
-
-Huang CW, Tsai JJ, Huang CC, Wu SN. Experimental and simulation
-studies on the mechanisms of levetiracetam-mediated inhibition of
-delayed-rectifier potassium current (KV3.1): contribution to the
-firing of action potentials.J Physiol Pharmacol (2009) in press.
-
-Levetiracetam (LEV) is an S-enantiomer pyrrolidone derivative with
-established antiepileptic efficacy in generalized epilepsy and partial
-epilepsy.  However, its effects on ion currents and membrane potential
-remain largely unclear.  In this study, we investigated the effect of
-LEV on differentiated NG108-15 neurons. In these cells treated with
-dibutyryl cyclic AMP, the expression level of the KV3.1 mRNA was
-elevated. With the aid of patch clamp technology, we found that LEV
-was able to suppress the amplitude of delayed rectifier K+ current
-(IK(DR)) in a concentration-dependent manner with an IC50 value of 37
-uM in differentiated NG108-15 neurons.  LEV (30 uM) shifted the
-steady-state activation of IK(DR) to a more positive potential by 10
-mV, without shifting the steady-state inactivation of IK(DR).  Neither
-Na+, nor erg (ether-a-go-go -related)-mediated K+ and ATP-sensitive K+
-currents were affected by LEV (100 uM).  LEV increased the duration of
-action potentials in current clamp configuration.  Simulation studies
-In a modified Hodgkin-Huxley neuron and network unraveled that the
-reduction of slowly inactivating IK(DR) resulted in membrane
-depolarization accompanied by termination of the firing of action
-potentials in a stochastic manner.  Therefore, the inhibitory effects
-on slowly inactivating IK(DR) (Kv3.1-encoded current) may constitute
-one of the underlying mechanisms through which LEV affects neuronal
-activity in vivo.
-
-
-To run the models:
-XPP: start with the command
-xppaut hh200x50-LEV01.ode
-(or similar)
-
-This simulation will make graphs similar to figure 10A in the paper of
-Huang et al.
-
-From Viewaxes, select Array, then assign to: column 1: VE0, Ncols:
-200, Row 1: 10, NRows: 200, Rowskip:10, Zmin: -90, Zmax: 40
-
-Back at the main menu select "Xi vs t", then change VE0 to VE4,
-finally select Initalconds -> Go to generate the following graphs:
-
-screenshot 2
-screenshot 1
-
-When gk3 was changed to 4 and eta to 10, graphs will be similar to
-Figure10B.
-
-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 College
-Tainan 70101, Taiwan
-snwu@mail.ncku.edu.tw
-