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:

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