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.
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
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
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
Natl Cheng Kung U Med Coll
Tainan 70101, Taiwan