<pre>
This is the readme.html for the models associated with the 
paper shown below:

Wu, S.-N. And H.-D. Chang (2005). "Diethyl pyrocarbonate, a 
histidine-modifying agent, directly stimulates activity of 
ATP-sensitive potassium channels in pituitary GH3 cells"
Biochem Pharm 2005 Dec 19; [Epub ahead of print].

ABSTRACT
The ATP-sensitive K(+) (K(ATP)) channels are composed of
sulfonylurea receptor and inwardly rectifying K(+) channel 
(Kir6.2) subunit. These channels are regulated by intracellular
ADP/ATP ratio and play a role in cellular metabolism. Diethyl 
pyrocarbonate (DEPC), a histidine-specific alkylating reagent, is
known to modify the histidine residues of the structure of 
proteins. The objective of this study was to determine whether 
DEPC modifies K(ATP)-channel activity in pituitary GH(3) cells. 
Steady-state fluctuation analyses of macroscopic K(+) current at 
-120mV produced power spectra that could be fitted with a single 
Lorentzian curve in these cells. The time constants in the 
presence of DEPC were increased. Consistent with fluctuation 
analyses, the mean open time of K(ATP)-channels was significantly
increased during exposure to DEPC. However, DEPC produced no
change in single-channel conductance, despite the ability of this
compound to enhance K(ATP)-channel activity in a concentration-
dependent manner with an EC(50) value of 16muM. DEPC-stimulated 
K(ATP)-channel activity was attenuated by pretreatment with 
glibenclamide. In current-clamp configuration, DEPC decreased the
firing of action potentials in GH(3) cells. A further application
of glibenclamide reversed DEPC- induced inhibition of spontaneous
action potentials. Intracellullar Ca(2+) measurements revealed 
the ability of DEPC to decrease Ca(2+) oscillations in GH(3) 
cells. Simulation studies also demonstrated that the increased 
conductance of K(ATP)-channels used to mimic DEPC actions reduced
the frequency of spontaneous action potentials and fluctuation of
intracellular Ca(2+). The results indicate that chemical 
modification with DEPC enhances K(ATP)-channel activity and 
influences functional activities of pituitary GH(3) cells.


To run the models:
XPP: start with the command

xpp ode\GH3_Katp

Mouse click on Initialconds, and then (G)o.
This makes a trace similar to fig 7 of the paper:

<img src="v_vs_t.jpg" alt="xpp image" width="400" height="300">

Regarding the xpp program, please visit Bard Ermentrout's website
<a href="http://www.pitt.edu/~phase/">http://www.pitt.edu/~phase/</a>
 which describes how to get and use xpp (Bard wrote xpp).

These model files were submitted by:

Dr. Sheng-Nan Wu, Han-Dong Chang
department of Physiology
National Cheng Kung University Medical College Tainan 70101, Taiwan

[email protected]
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