Actions of Rotenone on ionic currents and MEPPs in Mouse Hippocampal Neurons (Huang et al 2018)

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" ... With the aid of patch-clamp technology and simulation modeling, the effects of (Rotenone) Rot on membrane ion currents present in mHippoE-14 cells were investigated. Results: Addition of Rot produced an inhibitory action on the peak amplitude of INa ...; however, neither activation nor inactivation kinetics of INa was changed during cell exposure to this compound. Addition of Rot produced little or no modifications in the steady-state inactivation curve of INa. Rot increased the amplitude of Ca2+-activated Cl- current in response to membrane depolarization ... . Moreover, when these cells were exposed to 10 µM Rot, a specific population of ATP-sensitive K+ channels ... was measured, despite its inability to alter single-channel conductance. Under current clamp condition, the frequency of miniature end-plate potentials in mHippoE-14 cells was significantly raised in the presence of Rot (10 µM) with no changes in their amplitude and time course of rise and decay. In simulated model of hippocampal neurons incorporated with chemical autaptic connection, increased autaptic strength to mimic the action of Rot was noted to change the bursting pattern with emergence of subthreshold potentials. Conclusions: The Rot effects presented herein might exert a significant action on functional activities of hippocampal neurons occurring in vivo. "
1 . Huang CW, Lin KM, Hung TY, Chuang YC, Wu SN (2018) Multiple Actions of Rotenone, an Inhibitor of Mitochondrial Respiratory Chain, on Ionic Currents and Miniature End-Plate Potential in Mouse Hippocampal (mHippoE-14) Neurons. Cell Physiol Biochem 47:330-343 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism: Hippocampus;
Cell Type(s): Hippocampus CA3 pyramidal GLU cell;
Channel(s): I A; I Calcium; I K,Ca; I Na,t; I_KD;
Gap Junctions:
Simulation Environment: XPP;
Model Concept(s): Action Potentials; Bursting; Ephaptic coupling;
Implementer(s): Wu, Sheng-Nan [snwu at];
Search NeuronDB for information about:  Hippocampus CA3 pyramidal GLU cell; I Na,t; I A; I K,Ca; I Calcium; I_KD;
# Rotenone_ChemAut.ode
# Huange et al. Multiple actions of rotenone, an inhibitor of mitochondrial respiratory chain, 
# on ionic currents and minature end-plate potential in mouse hippocampal (mHippoE-14) neurons.
# Cell Physiol Biochem 2018;47:330-343.
# Chemical autaptic regulation
# tau=0.5
# init gaut=0
# dgaut/dt=0
para gaut=0.00005
para tau=5, kk=0
para kkk=1, theta=0, Vsyn=2
# n=5000
wiener b
# dv/dt=(I*100/(PI*2*rsoma*lsoma)-gna*h*(v-vna)*m^3-gkdr*nkdr^3*lkdr*(v+91) \
-gka*nka*lka*(v+91)-gkc*okc*(v+91)-gcat*0.001*nt32^2*lt32*(v-120)-gl*(v-vl)-gaut*(v-delay(v, tau)))/cm
dv/dt=(I*100/(PI*2*rsoma*lsoma)-gna*h*(v-vna)*m^3-gkdr*nkdr^3*lkdr*(v+91) \
ica(v) = gcat*0.001*nt32*nt32*lt32*(v-120)
# channel densities (Yilmaz and Ozer, Physica A, 2015 421:455-462)
para rhona=60, rhok=18, rhoca=10, nnna=100, nnk=80, nnca=50
# Na1.1 WT

# Cat3.1, 3.2, 3.3
# dnt31/dt=(nt31inf(v)-nt31)/taun31(v)
# dlt31/dt=(lt31inf(v)-lt31)/taul31(v)

# dnt33/dt=(nt33inf(v)-nt33)/taun33(v)
# dlt33/dt=(lt33inf(v)-lt33)/taul33(v)
# K dr
# K A
dnka/dt= ana(v)*(1-nka)-bna(v)*nka+kk*sqrt(((1-2*(ana(v)/(ana(v)+bna(v))))*nka+(ana(v)/(ana(v)+bna(v))))/(rhok*nnk))*b

dlka/dt= ala(v)*(1-lka)-bla*lka+kk*sqrt(((1-2*(ala(v)/(ala(v)+bla)))*lka+(ala(v)/(ala(v)+bla)))/(rhok*nnk))*b

# K C
  dokc/dt= ao(v)*(1-okc)-bo(v)*okc+kk*sqrt(((1-2*(ao(v)/(ao(v)+bo(v))))*okc+(ao(v)/(ao(v)+bo(v))))/(rhok*nnk))*b
# [Ca2+] dynamics
 dca/dt = 0.1*(-0.14*ica(v)-ca/5) 
# parameters
# par nt32=0, okc=0
par vna=50,vk=-91,gcat=5.0, i=0.02,  vl=-65
par gna=2,gkc=0.0004,gkdr=0.08,gka=0.0001,gl=1.6667e-5,cm=1e-3
num rm=60000, ra=200e-4, F=96520,F1=96.4853, R=8.3134, Temp=303.14
par cao=2,cai=5e-5
par rsoma=15, lsoma=25.5
par qt=1.18, q10na=1.62,q10m=3
# rate functions for ion channels
# SCN1A data from lossin et al., 2002
minf(v) =  1/(1+exp(-(v+26.4)/7.1))
hinf(v) =  1/(1+exp(-(v+67.5)/(-6.2)))
tauh(v) =  0.197+10.701/(1+exp((v+78.87)*0.0538))
# T-type Ca2+ channels
# CaT31
 nt31inf(v) = 1/(1+exp(-(v+49.3)/4.6))
 lt31inf(v) = 1/(1+exp((v+74.2)/5.5))
 taun31(v) = if(v>(-56))then((0.8+0.025*exp(-v/14.5))/qt)else((1.71*exp((v+120)/38))/qt)
 taul31(v) = (if(v>(-60))then((12.3+0.12*exp(-v/10.8))/qt)else(137/qt)) 
# CaT32
 nt32inf(v) = 1/(1+exp(-(v+48.4)/5.2))
 lt32inf(v) = 1/(1+exp((v+75.6)/6.2))
 taun32(v) = (if(v>=(-56))then((1.34+0.035*exp(-v/11.8))/qt)else((2.44*exp((v+120)/40))/qt))
 taul32(v) = (if(v>=(-60))then((18.3+0.005*exp(-v/6.2))/qt)else(500/qt))
# CaT33
 nt33inf(v) = 1/(1+exp(-(v+41.5)/6.2))
 lt33inf(v) = 1/(1+exp((v+69.8)/6.1))
 taun33(v) = (if(v>=(-60))then((7.2+0.02*exp(-v/14.7))/qt)else((0.875*exp((v+120)/41))/qt))
 taul33(v) = (if(v>=(-60))then((79.5+2.0*exp(-v/9.3))/qt)else(260/qt)) 
# K+  C
 ao(v) = ca*0.28/(ca+0.48e-3*exp(-2*0.84*v*F1/(R*Temp)))
 bo(v) = 0.48/(1+ca/(0.13e-6*exp(-2*v*F1/(R*Temp))))
# K+ DR
andr(v) = 0.03*exp(1e-3*2*(v+32)*F/(R*Temp))
bndr(v) = 0.03*exp(-1e-3*3*(v+32)*F/(R*Temp))
aldr(v) = 0.001*exp(-1e-3*2*(v+61)*F/(R*Temp))
bldr = 0.001
# K+ A
ana(v) = 0.02*exp(1e-3*1.8*(v+33.6)*F/(R*Temp))
bna(v) = 0.02*exp(-1e-3*1.2*(v+33.6)*F/(R*Temp))
ala(v) = 0.08*exp(-1e-3*4*(v+83)*F/(R*Temp))
bla = 0.08
init v=-65, ca=5e-5
init nkdr=0.00179769,lkdr=0.576006
init nka=0.026395,lka=0.0596601
 init okc=0.00337468
init h=0.9793
 init nt32=0.0394562
 init lt32=0.153206
# ina=gna*h*(v-vna)*m^3
# ikc=gkc*okc*(v+91)
# aux ina=ina
# aux ikc=ikc
# init nt31=0.0318903,lt31=0.158061,nt32=0.0394562,lt32=0.153206,nt33=0.0220894,lt33=0.312838
@ dt=0.001, bound=100000000, maxstor=10000000, total=100
# @ xp=gaut, xlo=0, xhi=0.002
@ ylo=-100, yhi=60, yp=v, delay=50, xlo=0, xhi=100
# @ poimap=period, poivar=v, poisgn=0, poistop=0
# @ rangeover=gaut. rangestep=200, ranglelow=0, rangehigh=0.002, rangeoldic=yes
# @ rangereset=no, lt=0
# @ output=Wuoutput.dat

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