ROS effects#
using ModelingToolkit
using OrdinaryDiffEq
using Plots
using CaMKIIModel
using CaMKIIModel: second, μM
Plots.default(lw=1.5)
Setup system#
Electrical stimulation starts at t=100 seconds and ends at t=300 seconds.
sys = build_neonatal_ecc_sys(simplify=true, reduce_iso=true, reduce_camk=true)
tend = 500.0second
prob = ODEProblem(sys, [], tend)
stimstart = 100.0second
stimend = 300.0second
@unpack Istim = sys
alg = FBDF()
FBDF(; max_order = Val{5}(), linsolve = nothing, nlsolve = OrdinaryDiffEqNonlinearSolve.NLNewton{Rational{Int64}, Rational{Int64}, Rational{Int64}, Rational{Int64}}(1//100, 10, 1//5, 1//5, false, true, 0//1), precs = DEFAULT_PRECS, κ = nothing, tol = nothing, extrapolant = linear, controller = Standard, step_limiter! = trivial_limiter!, autodiff = ADTypes.AutoForwardDiff(),)
No ROS#
callback = build_stim_callbacks(Istim, stimend; period=1second, starttime=stimstart)
@time sol = solve(prob, alg; callback)
7.826060 seconds (19.44 M allocations: 969.288 MiB, 4.40% gc time, 76.73% compilation time)
retcode: Success
Interpolation: 3rd order Hermite
t: 42230-element Vector{Float64}:
0.0
1.397037556582821e-7
9.238890872600831e-6
8.268743701533588e-5
0.0002916748356969014
0.0017327691557383657
0.0051472024471516595
0.009381914366487651
0.01412353770711788
0.02222607464446686
⋮
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430066.5613446226
442356.23657685495
454645.9118090873
466935.5870413197
481624.081564708
500000.0
u: 42230-element Vector{Vector{Float64}}:
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⋮
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[0.001470458466316511, 774.7561341614464, 775.0127500995218, 0.006887264089410047, 0.999662782589439, 0.9996647475774426, 0.0018324101878647568, 0.00268124372428502, 0.0017321766700635628, 0.0013738493695098118 … 0.12980850929084117, 0.12980831672443607, 0.12980812532328978, 0.12980793502499574, 0.12980774576962098, 0.12980755749958456, 0.12980737015954352, -69.08649804843239, 12969.874959870273, 151824.07982271194]
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i = (sys.t / 1000, sys.vm)
tspan=(298second, 300second)
plot(sol, idxs=i, title="Action potential"; tspan)
i = (sys.t / 1000, [sys.Cai_sub_SR, sys.Cai_sub_SL, sys.Cai_mean])
tspan=(298second, 300second)
plot(sol, idxs=i, title="Calcium transcient", label=["Ca (SR)" "Ca (SL)" "Ca (avg)"]; tspan)
i = (sys.t / 1000,sys.CaMKAct*100)
plot(sol, idxs=i, title="CaMKII", xlabel="Time (s)", ylabel="Active fraction (%)", label=false)
ROS 0.1uM#
prob2 = remake(prob, p=[sys.ROS => 0.1μM])
@time sol2 = solve(prob2, alg; callback)
1.761498 seconds (376.24 k allocations: 89.328 MiB, 2.52% gc time)
retcode: Success
Interpolation: 3rd order Hermite
t: 42215-element Vector{Float64}:
0.0
1.397037556582838e-7
9.238890871986907e-6
8.268743700514583e-5
0.0002916748356526253
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0.0051472024469624384
0.009381914366262189
0.014123537706870255
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⋮
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422661.8200913621
436206.5947048474
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470412.8286545167
486858.11591772886
500000.0
u: 42215-element Vector{Vector{Float64}}:
[0.0026, 830.0, 830.0, 0.00702, 0.966, 0.22156, 0.09243, 0.00188, 0.00977, 0.26081 … 0.12113, 0.12113, 0.12113, 0.12113, 0.12113, 0.12113, 0.12113, -68.79268, 13838.37602, 150952.75035000002]
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⋮
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[0.0015558164647984122, 776.7035415081775, 776.9756540096932, 0.00678377461961311, 0.9996786589262608, 0.9996805781514441, 0.001774870076380367, 0.0026372556908560215, 0.0017037445578363905, 0.0013280872065612509 … 0.13089770432181888, 0.1308974872319725, 0.13089727134859067, 0.13089705660334194, 0.1308968429306059, 0.13089663026734027, 0.1308964185529553, -69.30926794737157, 13071.790711198726, 151721.84289055192]
[0.001501236070978439, 775.4771497328928, 775.7393526779338, 0.006848623366184644, 0.9996687609966615, 0.999670440088497, 0.001810811855808103, 0.0026648148022135262, 0.0017215665843961744, 0.0013566716139774165 … 0.1302042716675315, 0.1302040691442929, 0.13020386782267193, 0.13020366763741403, 0.1302034685258484, 0.13020327042776159, 0.130203073285278, -69.16928325625143, 13007.37988625767, 151786.43921417996]
[0.0014569788934222661, 774.4289041185547, 774.6830718639211, 0.006904832648719196, 0.9996600405174357, 0.9996617650838487, 0.0018422725430210685, 0.0026887160597360905, 0.001737003444120276, 0.001381712200348224 … 0.12963324780068997, 0.12963305925035087, 0.12963287185678066, 0.12963268555858742, 0.12963250029681295, 0.12963231601481315, 0.12963213265814585, -69.04901104432314, 12953.048771663303, 151840.92698083847]
[0.001424989131186405, 773.6367157850724, 773.8850787612696, 0.006947781236484012, 0.9996533263247038, 0.9996550984016288, 0.0018664928472787066, 0.0027069818043607553, 0.0017488041951445896, 0.0014018656979971913 … 0.12921487830380157, 0.1292147015699464, 0.12921452597605138, 0.12921435146334428, 0.12921417797538037, 0.12921400545792835, 0.12921383385886276, -68.95776762717108, 12912.435831571775, 151881.6569065278]
i = (sys.t / 1000, sys.vm)
tspan=(298second, 300second)
plot(sol2, idxs=i, title="Action potential"; tspan)
i = (sys.t / 1000, [sys.Cai_sub_SR, sys.Cai_sub_SL, sys.Cai_mean])
tspan=(298second, 300second)
plot(sol2, idxs=i, title="Calcium transcient", label=["Ca (SR)" "Ca (SL)" "Ca (avg)"]; tspan)
i = (sys.t / 1000,sys.CaMKAct*100)
plot(sol2, idxs=i, title="CaMKII", xlabel="Time (s)", ylabel="Active fraction (%)", label=false)
ROS 1uM#
prob3 = remake(prob, p=[sys.ROS => 1μM])
@time sol3 = solve(prob3, alg; callback)
1.692673 seconds (376.26 k allocations: 89.285 MiB, 2.08% gc time)
retcode: Success
Interpolation: 3rd order Hermite
t: 42186-element Vector{Float64}:
0.0
1.3970375565856293e-7
9.23889078831287e-6
8.26874359097889e-5
0.0002916748311845054
0.001732769143620915
0.005147202427712317
0.009381914343437936
0.014123537681881076
0.022226074616217326
⋮
382027.1353878288
392293.568556618
402560.0017254072
412826.4348941964
423092.8680629856
439690.1616059812
460878.47559849976
482066.78959101834
500000.0
u: 42186-element Vector{Vector{Float64}}:
[0.0026, 830.0, 830.0, 0.00702, 0.966, 0.22156, 0.09243, 0.00188, 0.00977, 0.26081 … 0.12113, 0.12113, 0.12113, 0.12113, 0.12113, 0.12113, 0.12113, -68.79268, 13838.37602, 150952.75035000002]
[0.002599999989610171, 829.9999999963668, 829.9999999997507, 0.00702000000187161, 0.9660000000132074, 0.22156000002886056, 0.09242999998313912, 0.0018799999988577344, 0.009769999999149391, 0.2608099999679794 … 0.12113, 0.12113, 0.12113, 0.12113, 0.12113, 0.12113, 0.12113000000000024, -68.792680031212, 13838.376019997857, 150952.75035000042]
[0.0025999993129014044, 829.9999997597265, 829.9999999835165, 0.007020000123751708, 0.9660000008734306, 0.22156000190860706, 0.09242999888495675, 0.0018799999244530625, 0.0097699999437479, 0.2608099978824148 … 0.12113, 0.12113, 0.12113, 0.12113, 0.12113, 0.12113000000000013, 0.12113000000107572, -68.7926820643306, 13838.376019858315, 150952.75035002758]
[0.0025999938506275342, 829.9999978495804, 829.9999998524714, 0.00702000110615952, 0.9660000078171415, 0.2215600170819007, 0.09242999002044015, 0.0018799993234276927, 0.009769999496562813, 0.26080998104806385 … 0.12113, 0.12113, 0.12113, 0.12113, 0.12113000000000006, 0.12113000000007051, 0.12113000007858914, -68.7926984898246, 13838.376018731426, 150952.7503502467]
[0.002599978309412639, 829.99999241462, 829.9999994795787, 0.0070200038900499855, 0.9660000275744645, 0.22156006025534353, 0.09242996479772166, 0.0018799976097917568, 0.00976999822428434, 0.2608099331507847 … 0.12113, 0.12113, 0.12113, 0.12113000000000002, 0.12113000000000576, 0.12113000000223507, 0.121130000852223, -68.79274533954155, 13838.3760155209, 150952.7503508702]
[0.0025998711629486564, 829.9999549392155, 829.9999969077643, 0.007020022837590995, 0.9660001638127262, 0.22156035796214557, 0.09242979087191872, 0.0018799857164703906, 0.00976998945385259, 0.26080960292428107 … 0.12113000000000097, 0.12113000000000097, 0.12113000000000125, 0.12113000000002516, 0.12113000000216383, 0.1211300001916537, 0.12113001777018446, -68.79307067198195, 13838.375993299638, 150952.75035517072]
[0.0025996174748747396, 829.9998661650887, 829.9999908095883, 0.0070200654253408275, 0.96600048660277, 0.22156106332737285, 0.09242937878432356, 0.0018799568224820006, 0.009769968698884562, 0.2608088210117723 … 0.1211300000000009, 0.12113000000000299, 0.12113000000008202, 0.12113000000306805, 0.12113000011553023, 0.12113000431268632, 0.12113015716639577, -68.7938599072072, 13838.375939979878, 150952.7503653596]
[0.0025993031657983346, 829.9997560966418, 829.9999832373774, 0.007020113911265051, 0.9660008869322482, 0.2215619381456896, 0.09242886769859482, 0.0018799196342847253, 0.009769943005367937, 0.2608078522094791 … 0.12113000000000203, 0.12113000000003636, 0.12113000000104966, 0.12113000003007161, 0.12113000082696548, 0.1211300213614626, 0.12113049658039393, -68.79486714535219, 13838.375872817292, 150952.75037800003]
[0.002598951654137041, 829.9996328957303, 829.9999747462327, 0.007020162390972183, 0.9660013351731133, 0.2215629176793062, 0.09242829543547758, 0.0018798761691363405, 0.009769914300714052, 0.2608067687331526 … 0.12113000000001277, 0.12113000000029191, 0.12113000000687821, 0.12113000015542216, 0.12113000330022987, 0.12113006391159949, 0.1211310680350359, -68.7960239979059, 13838.37579655818, 150952.75039215852]
[0.002598351996848543, 829.9994224741127, 829.9999602043813, 0.007020230894952082, 0.9660021011082504, 0.22156459150735397, 0.09242731754981137, 0.0018797973748461184, 0.009769865410697175, 0.2608049205114231 … 0.12113000000017381, 0.12113000000318754, 0.1211300000566281, 0.12113000095596348, 0.1211300149807049, 0.1211302096587946, 0.12113244244516369, -68.79805585622643, 13838.37566424359, 150952.75041636516]
⋮
[0.0018477741349754498, 782.2220628078525, 782.5474894901955, 0.006498353024239923, 0.9997195526230267, 0.9997149213808217, 0.0016209749307196767, 0.00251627156031766, 0.0016255734874985996, 0.0012035826061009372 … 0.13445679558742685, 0.13445649891521225, 0.13445620330851557, 0.13445590868573953, 0.13445561496852151, 0.13445532208157504, 0.13445502995254024, -69.94159959955246, 13379.76685105905, 151412.99776862946]
[0.00179547831551821, 781.3491669245227, 781.665029022155, 0.006543328112318887, 0.9997133521978971, 0.9997131782181462, 0.0016447535534666671, 0.0025353073676170515, 0.0016378736840363182, 0.0012226218359973136 … 0.13383777844560887, 0.13383749443529014, 0.1338372115360259, 0.13383692966786745, 0.13383664875403467, 0.1338363687207607, 0.13383608949714587, -69.84015147095943, 13328.472378041302, 151464.4380779598]
[0.001746878852366633, 780.4949358953729, 780.8019197645312, 0.006587170373209723, 0.999707217835588, 0.9997089920065328, 0.001668102873984181, 0.002553874525714725, 0.0016498711359211214, 0.0012413441086341205 … 0.13325615825436377, 0.1332558868946285, 0.13325561667309452, 0.1332553475118289, 0.1332550793359875, 0.13325481207366305, 0.13325454565574307, -69.74192180392953, 13279.499897524012, 151513.5506850293]
[0.0017017652070280467, 779.6649713082315, 779.963716349227, 0.006629887077456336, 0.9997011547260578, 0.9997033080296314, 0.0016910137612359138, 0.002571975190291431, 0.001661567257310552, 0.001259740859518137 … 0.13270998121402122, 0.13270972153296065, 0.13270946301425532, 0.13270920558186453, 0.13270894916276085, 0.1327086936867827, 0.13270843908649504, -69.64683664538181, 13232.748295536487, 151560.43643462952]
[0.001659854287818514, 778.860044347481, 779.1511384692651, 0.0066714799127695085, 0.9996951687317851, 0.9996972536809634, 0.0017134743083837675, 0.0025896092070762378, 0.0016729619459533375, 0.0012778012058273843 … 0.13219694240687382, 0.13219669363554634, 0.13219644604815992, 0.132196199570466, 0.13219595413115828, 0.1321957096617286, 0.13219546609633112, -69.55483609738494, 13188.117730679724, 151605.1953452495]
[0.0015982108115663557, 777.6118114658988, 777.891663713513, 0.0067363264566735566, 0.9996856722423216, 0.9996874931360571, 0.001748793234025796, 0.0026171207078275307, 0.0016907395077540737, 0.0013062516359082714 … 0.13143241491615107, 0.131432182840845, 0.1314319519674783, 0.13143172222484895, 0.1314314935445765, 0.1314312658609636, 0.13143103911086584, -69.41253057107227, 13120.23639514505, 151673.27244223733]
[0.001529151089370261, 776.1145503164652, 776.3818282592418, 0.006814882793249523, 0.9996738984692258, 0.9996756614429761, 0.0017920665310030843, 0.0026504788845539665, 0.0017122953420340514, 0.0013411909610696936 … 0.13056109466481466, 0.130560882777284, 0.13056067209049332, 0.13056046253738143, 0.13056025405354446, 0.13056004657710565, 0.1305598400485926, -69.24194565892799, 13040.679075532973, 151753.0597792503]
[0.0014693504826125258, 774.7259033833303, 774.9823145402997, 0.0068888140361468, 0.9996625440821781, 0.999664334656839, 0.0018332799978617465, 0.0026819026291136296, 0.0017326013959716303, 0.0013745509617397631 … 0.12979326030352678, 0.12979306749745234, 0.12979287586536245, 0.1297926853446178, 0.12979249587506092, 0.12979230739889486, 0.12979211986056832, -69.08318722559665, 12968.390349824636, 151825.55763001408]
[0.0014249559528566554, 773.6347316551912, 773.8830893464979, 0.00694786556685293, 0.9996532820170392, 0.9996550339515151, 0.0018665394179816924, 0.0027070223947584897, 0.0017488340617034031, 0.0014015311335320987 … 0.12921452093036181, 0.12921434324761466, 0.12921416670332894, 0.12921399123865368, 0.1292138167970696, 0.12921364332427523, 0.12921347076807876, -68.95758854637617, 12912.376962207336, 151881.73278911083]
i = (sys.t / 1000, sys.vm)
tspan=(298second, 300second)
plot(sol3, idxs=i, title="Action potential"; tspan)
i = (sys.t / 1000, [sys.Cai_sub_SR, sys.Cai_sub_SL, sys.Cai_mean])
tspan=(298second, 300second)
plot(sol3, idxs=i, title="Calcium transcient", label=["Ca (SR)" "Ca (SL)" "Ca (avg)"]; tspan)
i = (sys.t / 1000,sys.CaMKAct*100)
plot(sol3, idxs=i, title="CaMKII", xlabel="Time (s)", ylabel="Active fraction (%)", label=false)
Comparisons#
i = (sys.t / 1000,sys.CaMKAct*100)
plot(sol, idxs=i, title="Active CaMKII", lab="ROS 0uM")
plot!(sol2, idxs=i, lab="ROS 0.1uM")
plot!(sol3, idxs=i, lab="ROS 1uM", xlabel="Time (s)", ylabel="Active fraction (%)")
This notebook was generated using Literate.jl.