Effects of isoproterenol

Contents

Effects of isoproterenol#

using ModelingToolkit
using OrdinaryDiffEq
using Plots
using CaMKIIModel
using CaMKIIModel: second, μM
Plots.default(lw=1.5)

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
alg = TRBDF2()

TRBDF2(; 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, smooth_est = true, extrapolant = linear, controller = PI, step_limiter! = trivial_limiter!, autodiff = ADTypes.AutoForwardDiff(),)

Without isoproterenol#

@unpack Istim = sys
callback = build_stim_callbacks(Istim, stimend; period=1second, starttime=stimstart)
@time sol = solve(prob, alg; callback)

  9.982731 seconds (21.47 M allocations: 1.005 GiB, 3.48% gc time, 74.00% compilation time)

retcode: Success
Interpolation: 3rd order Hermite
t: 22357-element Vector{Float64}:
      0.0
      0.00037376965588217846
      0.004111466214703963
      0.03981907054375368
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      0.1655435225566852
      0.2409336011179059
      0.5227875405036884
      1.0858597487365014
      2.388889121726196
      ⋮
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u: 22357-element Vector{Vector{Float64}}:
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 ⋮
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i = (sys.t/1000, sys.vm)
plot(sol, idxs=i, tspan=(295second, 300second), title="Action potential", xlabel="Time (s)")

_images/51a6a085672226a4f8959854ae4c053e688a14fe81b73aa489c2a55ab48f4c5b.png

plot(sol, idxs=(sys.t/1000, [sys.Cai_sub_SR, sys.Cai_sub_SL, sys.Cai_mean]), tspan=(299second, 300second), title="Calcium transcient", xlabel="Time (s)", ylabel="Conc. (μM)", label=["Ca (SR)" "Ca (SL)" "Ca (avg)"])

_images/49b038a2098c6c16a60350c308fb703ef17b23f19194809b31a99d3139eca958.png

plot(sol, idxs=(sys.t/1000, sys.CaMKAct*100), title="Active CaMKII", label=false, ylabel="Active fraction (%)" , xlabel="Time (s)")

_images/12841d234398704beab7e0531b865444790f7139bdc6aff812eb03c86829ec65.png

0.1uM isoproterenol#

prob2 = remake(prob, p=[sys.ISO => 0.1μM])
sol2 = solve(prob2, alg; callback)

retcode: Success
Interpolation: 3rd order Hermite
t: 24672-element Vector{Float64}:
      0.0
      0.0003737343848581722
      0.004111078233439894
      0.039816339706127295
      0.060900752777357826
      0.16553476226263736
      0.24091875673065616
      0.5229648546728856
      1.0863777736793474
      2.413405322158768
      ⋮
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 482835.17229020357
 485399.71347236686
 488504.4036737538
 490428.8143975678
 494101.0270270934
 497730.1337078878
 500000.0
u: 24672-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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 [0.005743572333224127, 923.4735705931561, 924.6742838535378, 0.006897324476534978, 0.9996612740854697, 0.999663585304905, 0.0018376449860658171, 0.0026855234434519405, 0.0017349171243682328, 0.001377902683490218  …  0.11869231908159746, 0.11869222608673441, 0.1186921309749277, 0.11869203376936838, 0.11869193449233148, 0.1186918331652211, 0.11869172980861259, -69.06501911991934, 13142.048290081042, 151639.89002302237]
 [0.005729115688636965, 923.4822554983314, 924.6799549758315, 0.006905637858277505, 0.9996599771524922, 0.9996622835187406, 0.0018423139516549308, 0.0026890591344633803, 0.0017372018436868464, 0.0013816864770471377  …  0.11861420752251509, 0.11861411534779287, 0.11861402108508094, 0.11861392475715603, 0.11861382638589502, 0.11861372599231906, 0.11861362359663516, -69.04729441284292, 13134.47314666589, 151647.47592739473]
 [0.005702045470588575, 923.497830210579, 924.689885347638, 0.0069213857720900164, 0.999657511590779, 0.9996598077387568, 0.0018511731843121966, 0.00269575772743837, 0.0017415303151434825, 0.0013888691292035277  …  0.11846780087192706, 0.11846771031489882, 0.11846761772554275, 0.11846752312585955, 0.11846742653698074, 0.11846732797921145, 0.11846722747207046, -69.0137766590543, 13120.205588309898, 151661.7637296896]
 [0.0056759401827787565, 923.5120042610863, 924.6986149625337, 0.006936807444601013, 0.9996550853261155, 0.9996573715954428, 0.0018598688325022828, 0.002702318796293575, 0.0017457698875930476, 0.001395922239639727  …  0.11832643138804004, 0.11832634243272859, 0.11832625149963494, 0.11832615861000148, 0.11832606378423154, 0.11832596704193057, 0.11832586840194499, -68.98102643758686, 13106.338150055893, 151675.6508073154]
 [0.005659933592529468, 923.5202679462639, 924.7035398230626, 0.00694638216622596, 0.9996535729537314, 0.9996558531099955, 0.0018652782199450868, 0.002706392926629499, 0.001748402491504242, 0.0014003115950622016  …  0.11823966507242743, 0.11823957709410846, 0.11823948717098028, 0.11823939532382692, 0.1182393015726114, 0.11823920593651596, 0.1182391084339801, -68.9607295128334, 13097.780517104387, 151684.22054028572]

plot(sol2, idxs=(sys.t/1000, sys.vm), tspan=(295second, 300second), title="Action potential", xlabel="Time (s)")

_images/a12021eea466494e8d4b4619e4b11fd41e1db0bab836c368e547b4e7211d7d16.png

plot(sol2, idxs=(sys.t/1000, [sys.Cai_sub_SR, sys.Cai_sub_SL, sys.Cai_mean]), tspan=(299second, 300second), title="Calcium transcient", xlabel="Time (s)", ylabel="Conc. (μM)", label=["Ca (SR)" "Ca (SL)" "Ca (avg)"])

_images/18c0a9a0c14f1143ddc03e83d8008563079c1558b4baaa6a3877f91e595bfbd8.png

plot(sol2, idxs=(sys.t/1000, sys.CaMKAct*100), title="Active CaMKII", label=false, ylabel="Active fraction (%)" , xlabel="Time (s)")

_images/1f3f4ed6530889b69c54c6048fa9a403fb28bdcf4d25343b4c22fc3a594c9554.png

Comparison#

i = (sys.t/1000, sys.Cai_mean * 1000)
tspan = (299second, 300second)
plot(sol, idxs=i, title="Calcium transcient", lab="ISO (0uM)"; tspan)
plot!(sol2, idxs=i, lab="ISO (0.1uM)", xlabel="Time (s)", ylabel="Conc. (μM)"; tspan)

_images/48ea0388420892477b4d10b957d3cb155ae0bf3296aaea912d4b9c707cd3a634.png

i = (sys.t/1000, sys.CaMKAct*100)
plot(sol, idxs=i, title="Active CaMKII", lab="ISO (0uM)")
plot!(sol2, idxs=i, lab="ISO (0.1uM)", ylabel="Active fraction (%)" , xlabel="Time (s)")

_images/312ed72bfd1365070dd068e8177a1ce5d4d5daeadbf21f1a0cf09e468fe0c095.png

i = (sys.t/1000, sys.vm)
plot(sol, idxs=i, tspan=(297second, 300second), title="Action potential", lab="ISO (0uM)")
plot!(sol2, idxs=i, tspan=(297second, 300second), lab="ISO (1uM)", xlabel="Time (ms)", ylabel="Voltage (mV)")

_images/579e2cf693710e7fc67f6120e02125b09172e555714220643282ab5d7a6a39c3.png

This notebook was generated using Literate.jl.