This is the readme-txt for allosteric kinetic model associated with the paper.

Horrigan FT, Cui J, Aldrich RW. Allosteric voltage gating of potassium channels I: mSlo ionic currents in the absence of Ca2+. J Gen Physiol 1999;114:277-304.

Abstract: Activation of large conductance Ca(2+)-activated K(+) channels is controlled by both cytoplasmic Ca(2+) and membrane potential. To study the mechanism of voltage-dependent gating, we examined mSlo Ca(2+)-activated K(+) currents in excised macropatches from Xenopus oocytes in the virtual absence of Ca(2+) (<1 nM). In response to a voltage step, I(K) activates with an exponential time course, following a brief delay. The delay suggests that rapid transitions precede channel opening. The later exponential time course suggests that activation also involves a slower rate-limiting step. However, the time constant of I(K) relaxation [tau(I(K))] exhibits a complex voltage dependence that is inconsistent with models that contain a single rate limiting step. tau(I(K)) increases weakly with voltage from -500 to -20 mV, with an equivalent charge (z) of only 0.14 e, and displays a stronger voltage dependence from +30 to +140 mV (z = 0.49 e), which then decreases from +180 to +240 mV (z = -0.29 e). Similarly, the steady state G(K)-V relationship exhibits a maximum voltage dependence (z = 2 e) from 0 to +100 mV, and is weakly voltage dependent (z congruent with 0.4 e) at more negative voltages, where P(o) = 10(-5)-10(-6). These results can be understood in terms of a gating scheme where a central transition between a closed and an open conformation is allosterically regulated by the state of four independent and identical voltage sensors. In the absence of Ca(2+), this allosteric mechanism results in a gating scheme with five closed (C) and five open (O) states, where the majority of the channel's voltage dependence results from rapid C-C and O-O transitions, whereas the C-O transitions are rate limiting and weakly voltage dependent. These conclusions not only provide a framework for interpreting studies of large conductance Ca(2+)-activated K(+) channel voltage gating, but also have important implications for understanding the mechanism of Ca(2+) sensitivity.

To run the models: XPP: start with the command

xpp ode\IKCa_HCA.ode

For a simple run: Mouse click on Initialconds, and then (G)o.

To reproduce traces similar to fig 6A of the paper:

Click "Erase" to clear the graph To run the series of voltage-clamp studies, click Initialconds -> Range over, change to 'vtest', and then select voltage protocol from Steps 10 Start 80 End 240 Reset Storage Y Use old ic's Y Cycle color Y

When you click OK the voltage clamp family will be simulated.

The scheme IX kinetic parameters were shown in Table 1 of the paper.

Regarding xpp program, please contact with Bard Ermentrout's website http://www.pitt.edu/~phase/ describes how to get and use xpp.

These model files were submitted by:

Dr. Sheng-Nan Wu, Han-Dong Chang, and Jiun-Shian Wu Dept Physiol Natl Cheng Kung U Med Coll Tainan 70101, Taiwan

snwu@mail.ncku.edu.tw