TITLE ichan2.mod combination of Nav and Kv channels for Hodgin-Huxely-type action potential mechanism
COMMENT
Original Mod File:
Original name 'ichan2.mod'
Santhakumar V, Aradi I, Soltesz I (2005) J Neurophysiol 93:437-53
https://senselab.med.yale.edu/modeldb/ShowModel.cshtml?model=51781&file=%2fdentategyrusnet2005%2fichan2.mod
Morgan RJ, Soltesz I (2008) Proc Natl Acad Sci U S A 105:6179-84
Morgan RJ, Santhakumar V, Soltesz I (2007) Prog Brain Res 163:639-58
Cutsuridis V, Cobb S, Graham BP (2009) Hippocampus 20(3):423-46
Current version by A. Hanuschkin <AH, 2011> for:
Yim MY, Hanuschkin A, Wolfart J (2015) Hippocampus 25:297-308.
http://onlinelibrary.wiley.com/doi/10.1002/hipo.22373/abstract
Changes in current versus original version:
- added a tonic (leak) GABAA conductance to be modified during epilepsy (see Young CC, Stegen M, Bernard R, Muller M, Bischofberger J, Veh RW, Haas CA, Wolfart J (2009) J Physiol 587:4213-4233)
- checked, simplified (reduced to single k Ion, Ekf=Eks=Ek) & commented by A. Hanuschkin 2011,2012
Mod File history:
I_Na: (equivalent to Santhakumar et al 2005)
* modified parameters (shifted voltage dependence by 68mV)
Aradi I and Soltesz I (2002) J Physiol. 538(Pt 1):227-51.
* dynamics (NOTE in this paper (at least) sign error in alpha_m, beta_m and alpha_n! (1-exp()) -> should be (exp()-1) <ah>)
Aradi and Soltesz (2002)
* modified from
Yuen GL, Durand D, (1991) Neuroscience 41(2-3):411-23.
* Aradi and Soltesz (2002) parameters =
Aradi I, Holmes WR (1999) J Comput Neurosci 6:215-35
parameters =
Yuen and Durand (1991) parameters + V shift of 16mV
I_Kf: (equivalent to Santhakumar et al 2005)
* modified parameters Aradi and Soltesz (2002)/Aradi & Holmes (1999) (shifted voltage dependence by 65mV)
* NOTE typo in formular beta_n in Aradi and Soltesz (2002): beta_n = 0.264/exp((v-22)/4) -> should be beta_n = 0.264/exp((v-22)/40) <ah>
* modified parameters from Yuen and Durand (1991)
I_Ks: (equivalent to Santhakumar et al 2005)
* modified parameters Aradi & Holmes (1999) (shifted voltage dependence by 65mV)
I_leak: (equivalent to Santhakumar et al 2005)
I_GABAA: (tonic GABAA leak (see above), added in Yim et al (2015))
* replicated from I_leak
A. Hanuschkin(c) 2011,2012
ENDCOMMENT
UNITS {
(mA) =(milliamp)
(mV) =(millivolt)
(uF) = (microfarad)
(molar) = (1/liter)
(nA) = (nanoamp)
(mM) = (millimolar)
(um) = (micron)
FARADAY = 96520 (coul)
R = 8.3134 (joule/degC)
}
NEURON {
: "suffix marks the mechanism to be distributed and whose variables & parameters are identified in hoc by a particular suffix" The Neuron Book Chap 9.5
SUFFIX ichan2
: ION usage block
USEION na READ ena WRITE ina VALENCE 1 : Na current
USEION k READ ek WRITE ik : K current
NONSPECIFIC_CURRENT il, igabaa : leak current
: range variable definition block,
: i.e. variables that might change with space along a compartment / could be declared global in this case
RANGE gnatbar, gkfbar, gksbar : gbar values for Na, K(slow/fast)
RANGE gl, el, ina, ik, il, ggabaa, igabaa, egabaa : gbar and reversal poti for leak current
}
: The INDEPENDENT statement was omitted; INDEPENDENT statements are irrelevant to NEURON. http://www.neuron.yale.edu/phpbb/viewtopic.php?f=16&t=2351
: INDEPENDENT {t FROM 0 TO 100 WITH 100 (ms)}
: Variables whose values are normally specified by the user are parameters, and are declared in a PARAMETER block.
: Variables in the parameter section will have global scope
PARAMETER {
:v (mV)
:celsius = 6.3 (degC)
:dt (ms)
gnatbar (mho/cm2) : Na (gbar and reversal poti)
ena (mV)
gkfbar (mho/cm2) : K (gbar(slow/fast), reversal is ek)
gksbar = 0 (mho/cm2) : init to 0 (not included in BC, HIPP and MC) <ah>
ek (mV)
gl (mho/cm2) : leak (gbar and reversal poti)
el (mV)
ggabaa (mho/cm2) : GABAA (gbar and reversal poti)
egabaa (mV)
}
: "If a model involves differential equations [..] their dependent variables or unknowns are to be listed in the STATE block" The Neuron Book Chap 9.5
STATE {
m h nf ns
}
: The ASSIGNED block is used to declare two kinds of variables
: 1) those given values outside the mod file (variables potentially available to every mechanism (e.g. v, celsius,t..)
: 2) left hand side of assignment statements (unknowns in set of equations, dependent variables in differential euqtions ...)
ASSIGNED {
: 1)
v (mV)
celsius (degC)
dt (ms)
: 2)
gna (mho/cm2) : Na
ina (mA/cm2)
gkf (mho/cm2) : K
gks (mho/cm2)
ik (mA/cm2)
il (mA/cm2) : leak
igabaa (mA/cm2) : GABAA
minf hinf nfinf nsinf : left hand side of differential equations
mtau (ms) htau (ms) nftau (ms) nstau (ms) : and other assignment variables
mexp hexp nfexp nsexp
q10
}
: This block is evaluated every time step.
BREAKPOINT {
SOLVE states : here the state variables are updated
gna = gnatbar*m*m*m*h : calculated g at timepoint t
gkf = gkfbar*nf*nf*nf*nf
gks = gksbar*ns*ns*ns*ns
ina = gna*(v - ena) : calculated currents flowing
ik = gkf*(v-ek) + gks*(v-ek)
il = gl*(v-el)
igabaa = ggabaa*(v-egabaa)
}
: UNITSOFF
: Called from Neuron during initializing the model
INITIAL {
trates(v)
m = minf
h = hinf
nf = nfinf
ns = nsinf
}
: discreticed versions of the differential equations, hence a PROCEDURE and not DERIVATIVE block
PROCEDURE states() { : Computes state variables m, h, and n
trates(v) : at the current v and dt.
m = m + mexp*(minf-m)
h = h + hexp*(hinf-h)
nf = nf + nfexp*(nfinf-nf)
ns = ns + nsexp*(nsinf-ns)
}
: moved this to assign block <ah>
: LOCAL q10
:Computes rate and other constants at current v.
PROCEDURE rates(v) {
LOCAL alpha, beta, sum
q10 = 3^((celsius - 6.3)/10)
:"m" sodium activation system - act and inact cross at -40 : shifted by 68mV compared to in Aradi 1999/2002
alpha = -0.3*vtrap((v+60-17),-5) : in Aradi 1999: alpha = -0.3*vtrap((v-25),-5); in Aradi 2002: alpha = 0.3*vtrap((v-25),-5) <ah>
beta = 0.3*vtrap((v+60-45),5) : in Aradi 1999: beta = 0.3*vtrap((v-53),5); in Aradi 2002: beta = -0.3*vtrap((v-53),5) <ah>
sum = alpha+beta
mtau = 1/sum minf = alpha/sum
:"h" sodium inactivation system : shifted by 68mV compared to in Aradi 1999/2002
alpha = 0.23/exp((v+60+5)/20) : in Aradi 1999/2002: alpha = 0.23/exp((v-3)/20) <ah>
beta = 3.33/(1+exp((v+60-47.5)/-10)) : in Aradi 1999/2002: beta = 3.33/(1+exp((v-55.5)/-10)) <ah>
sum = alpha+beta
htau = 1/sum
hinf = alpha/sum
:"ns" sKDR activation system : shifted by 65mV compared to Aradi 1999 <ah>
alpha = -0.028*vtrap((v+65-35),-6) : in Aradi 1999: alpha = -0.028*vtrap((v-35),-6)
beta = 0.1056/exp((v+65-10)/40) : in Aradi 1999: beta = 0.1056/exp((v-10)/40)
sum = alpha+beta
nstau = 1/sum nsinf = alpha/sum
:"nf" fKDR activation system : shifted by 65mV compared to Aradi 1999/2002 <ah>
alpha = -0.07*vtrap((v+65-47),-6) : in Aradi 1999: alpha = -0.07*vtrap((v-47),-6); in Aradi 2002: alpha = 0.07*vtrap((v-47),-6) <ah>
beta = 0.264/exp((v+65-22)/40) : in Aradi 1999/2002: beta = 0.264/exp((v-22)/40) // probably typo in Aradi & Soltez 2002 there: beta = 0.264/exp((v-22)/4) <ah>
sum = alpha+beta
nftau = 1/sum nfinf = alpha/sum
}
: Computes rate and other constants at current v.
PROCEDURE trates(v) {
LOCAL tinc
: TABLE minf, mexp, hinf, hexp, nfinf, nfexp, nsinf, nsexp, mtau, htau, nftau, nstau : <ah>
: DEPEND dt, celsius FROM -100 TO 100 WITH 200 : <ah>
rates(v) : not consistently executed from here if usetable_hh == 1
: so don't expect the tau values to be tracking along with
: the inf values in hoc
tinc = -dt * q10
mexp = 1 - exp(tinc/mtau)
hexp = 1 - exp(tinc/htau)
nfexp = 1 - exp(tinc/nftau)
nsexp = 1 - exp(tinc/nstau)
}
:Traps for 0 in denominator of rate eqns.
FUNCTION vtrap(x,y) {
if (fabs(x/y) < 1e-6) {
vtrap = y*(1 - x/y/2)
}else{
vtrap = x/(exp(x/y) - 1)
}
}
:UNITSON