strdef cmd, isomer
objref vbox1, vbox2, vbox3 // graphs variables
objref gv1, gi2, gi3 // graphs variables
objref volt_cl // variable for Point-Process
objref peak_vec // vector for the peak current
objref v_vec // vector for the steps of voltage clamping
create soma
soma {
diam = 50 // micron
L = 63.66198 // micron, so that area = 10000 micron2
nseg = 1 // dimensionless
cm = 1 // uF/cm2
Ra = 70 // ohm-cm
volt_cl = new VClamp_plus(.5)
}
y_min = -0.9 // variable for the maximum peak (graphic)
displ = 0 // current and voltage curves not showed (0), or
// showed (1) during the simulation
incr = 5 // step increment
dens = 0 // initializing clamping current
cl_st = -140
cl_end = 0
peak_vec = new Vector()
v_vec = new Vector()
soma volt_cl=new VClamp_plus(.5)
proc Clamp() {
peak_curr = 0 // inizializzazione del valore della corrente di picco
volt_cl.amp[1] = $1 // mV
finitialize(hold_pot)
while (t<tstop) {
dens=volt_cl.i/area(.5)*100-soma.i_cap(.5) // clamping current in mA/cm2,
// subtracted the capacitive current
if (displ==1) {
gv1.line(t, soma.v(.5))
gv1.flush()
gi2.line(t, dens)
gi2.flush()
}
if (t>(dur_st_cond+10)) {
if (abs(dens)>peak_curr) {
peak_curr=abs(dens)
}
}
fadvance()
}
peak_vec.append(peak_curr)
v_vec.append($1)
print peak_curr, $1 // debugging
doEvents()
}
// erasing graphics 1 and 2
proc erase() {
gv1.erase(0)
gi2.erase(0)
gv1.size(0, tstop, cl_st, cl_end)
gi2.size(dur_st_cond+10, dur_st_cond+30, y_min, 0.1)
gv1.beginline()
gi2.beginline(2,1)
}
proc start() {
peak_vec.resize(0)
v_vec.resize(0)
Tstop()
for (i=cl_st; i<=cl_end; i=i+incr) {
Clamp(i)
erase()
}
peak_norm = peak_vec.max()
for i=0, peak_vec.size()-1 {
peak_vec.x[i]=peak_vec.x[i]/peak_norm
}
gi3.erase()
gi3.size(cl_st-10, cl_end+10, 0, 1)
gi3.begin()
peak_vec.line(gi3,v_vec,1,1)
for i=0, peak_vec.size()-1 {
gi3.flush()
doNotify()
}
}
proc change_isomer() {
num_to_strg(num_iso)
sprint (cmd, "%s %s", "uninsert", isomer)
execute(cmd)
num_to_strg(nw_num_iso)
sprint (cmd, "%s %s", "insert", isomer)
execute(cmd)
num_iso = nw_num_iso
}
proc num_to_strg() {
if ($1 == 1) {
isomer = "na11a"
y_min=-0.9
hold_pot = -120 // holding potential
dur_st_cond = 100 // duration of the conditioning stimulus
dur_st_test = 20 // test stimulus duration
amp_st_test = -10 // test stimulus amplitude
cl_st = -140 // voltage-clamp starting value
cl_end = 0 // voltage-clamp ending value
}
if ($1 == 2) {
isomer = "na12a"
y_min=-0.9
hold_pot = -120
dur_st_cond = 100
dur_st_test = 20
amp_st_test = -10
cl_st = -140
cl_end = -10
}
if ($1 == 3) {
isomer = "na13a"
y_min=-0.9
hold_pot = -90
dur_st_cond = 1000
dur_st_test = 20
amp_st_test = -10
cl_st = -100
cl_end = 15
}
if ($1 == 4) {
isomer = "na14a"
y_min=-0.8
hold_pot = -120
dur_st_cond = 100
dur_st_test = 50
amp_st_test = -10
cl_st = -140
cl_end = -20
}
if ($1 == 5) {
isomer = "na15a"
y_min=-1.1
hold_pot = -120
dur_st_cond = 500
dur_st_test = 20
amp_st_test = -10
cl_st = -120
cl_end = 0
}
if ($1 == 6) {
isomer = "na16a"
y_min=-1.7
hold_pot = -90
dur_st_cond = 1000
dur_st_test = 20
amp_st_test = 0
cl_st = -120
cl_end = 0
}
if ($1 == 7) {
isomer = "na17a"
y_min=-1.5
hold_pot = -140
dur_st_cond = 500
dur_st_test = 20
amp_st_test = -20
cl_st = -150
cl_end = -10
}
if ($1 == 8) {
isomer = "na18a"
y_min=-1.1
hold_pot = -70
dur_st_cond = 500
dur_st_test = 40
amp_st_test = 0
cl_st = -80
cl_end = 20
}
if ($1 == 9) {
isomer = "na19a"
y_min=-3.3
hold_pot = -120
dur_st_cond = 300
dur_st_test = 50
amp_st_test = -40
cl_st = -140
cl_end = 10
}
}
proc Tstop() {
volt_cl.dur[0] = 10 // ms
volt_cl.amp[0] = hold_pot // mV
volt_cl.dur[1] = dur_st_cond // ms
volt_cl.dur[2] = dur_st_test // ms
volt_cl.amp[2] = amp_st_test // mV
volt_cl.dur[3] = 10 // ms
volt_cl.amp[3] = hold_pot // mV
tstop = 0
for i=0, 3 {
tstop = tstop + volt_cl.dur[i]
}
}
access soma
num_iso = 1
nw_num_iso = num_iso
num_to_strg(num_iso)
sprint (cmd, "%s %s", "insert", isomer)
execute(cmd)
variable_domain("nw_num_iso", 1, 9)
{
xpanel("RunControl", 0)
hold_pot = -120
v_init = hold_pot
xvalue("Init","v_init", 1,"stdinit()", 1, 1 )
xbutton("Init & Run","run()")
xbutton("Stop","stoprun=1")
runStopAt = 5
xvalue("Continue til","runStopAt", 1,"{continuerun(runStopAt) stoprun=1}", 1, 1 )
runStopIn = 1
xvalue("Continue for","runStopIn", 1,"{continuerun(t + runStopIn) stoprun=1}", 1, 1 )
xbutton("Single Step","steprun()")
t = 140
xvalue("t","t", 2 )
tstop = 140
xvalue("Tstop","tstop", 1,"tstop_changed()", 0, 1 )
dt = 0.0125
xvalue("dt","dt", 1,"setdt()", 0, 1 )
steps_per_ms = 40
xvalue("Points plotted/ms","steps_per_ms", 1,"setdt()", 0, 1 )
screen_update_invl = 0.05
xvalue("Scrn update invl","screen_update_invl", 1,"", 0, 1 )
realtime = 0.00999999
xvalue("Real Time","realtime", 0,"", 0, 1 )
xpanel(3,102)
}
{
xpanel("Start", 0)
xbutton("Start","start()")
celsius=22
xvalue("celsius")
ena=65
xvalue("ena")
xvalue("isomer (1-9)","nw_num_iso",1,"change_isomer()")
hold_pot=v_init
volt_cl.amp[0]=hold_pot
xvalue("holding_pot", "volt_cl.amp[0]")
volt_cl.dur[0]=10
xvalue("dur_pre_cond", "volt_cl.dur[0]", 1, "Tstop()") // holding potential duration before conditioning stimulus
dur_st_cond = 100
xvalue("dur_st_cond", "dur_st_cond", 1, "Tstop()") // conditioning stimulus duration
amp_st_test = -10
xvalue("amp_st_test", "amp_st_test") // test stimulus amplitude
dur_st_test = 20
xvalue("dur_st_test", "dur_st_test", 1, "Tstop()") // test stimulus duration
volt_cl.amp[3]=hold_pot
xvalue("amp_post_test", "volt_cl.amp[3]")
volt_cl.dur[3]=10
xvalue("dur_post_test", "volt_cl.dur[3]", 1, "Tstop()") // holding potential duration after test stimulus
xvalue("starting_clamp", "cl_st")
xvalue("ending_clamp", "cl_end")
xvalue("incr", "incr")
xstatebutton("display", &displ) // displaying single stimuli during simulation
xpanel(280,102)
}
// graphic for soma voltage
vbox1=new VBox()
vbox1.intercept(1)
gv1=new Graph()
gv1.size(0, tstop, cl_st, cl_end)
vbox1.intercept(0)
vbox1.map("Membrane voltage", 3, 600, -1, 0)
// graphic for clamp current (clamp.i)
vbox2=new VBox()
vbox2.intercept(1)
gi2=new Graph()
gi2.size(dur_st_cond+10, dur_st_cond+30, y_min, 0.1)
vbox2.intercept(0)
vbox2.map("Soma clamp current", 550, 10, 500, 350)
// grafico per corrente di inattivazione normalizzata
vbox3=new VBox()
vbox3.intercept(1)
gi3=new Graph()
gi3.size(cl_st-10, cl_end+10, 0, 1)
vbox3.intercept(0)
vbox3.map("Normalized current-voltage relation", 550, 400, 500, 350)