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49 changes: 49 additions & 0 deletions README.md
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# 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.
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