diff --git a/README.md b/README.md new file mode 100644 index 0000000..8005b27 --- /dev/null +++ b/README.md @@ -0,0 +1,49 @@ +# Readme for the Models Associated with the Paper + +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 16 µM. + +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. Intracellular 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: + +![xpp image](v_vs_t.jpg) + +Regarding the xpp program, please visit Bard Ermentrout's website [http://www.pitt.edu/~phase/](http://www.pitt.edu/~phase/) which describes how to get and use xpp (Bard wrote xpp). + +--- + +## Model File Contributors + +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 + +snwu@mail.ncku.edu.tw + +--- + +2025-05-27 – Standardized to Markdown. \ No newline at end of file diff --git a/readme.html b/readme.html deleted file mode 100644 index d4f4d83..0000000 --- a/readme.html +++ /dev/null @@ -1,63 +0,0 @@ -
-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:
-
-xpp image
-
-Regarding the xpp program, please visit Bard Ermentrout's website
-http://www.pitt.edu/~phase/
- 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
-
-snwu@mail.ncku.edu.tw
-