Effects of isoproterenol

using ModelingToolkit
using OrdinaryDiffEq, SteadyStateDiffEq, DiffEqCallbacks
using Plots
using CSV
using DataFrames
using Dates
using CaMKIIModel
using CaMKIIModel: ms, μM
Plots.default(lw=1.5)

Setup model

@mtkcompile sys = build_neonatal_ecc_sys()
tend = 205* 1000ms
prob = ODEProblem(sys, [], tend)
stimstart = 30* 1000ms
stimend = 120* 1000ms
alg = KenCarp47()

Internal error: stack overflow in type inference of remake(SciMLBase.ODEProblem{Array{Float64, 1}, Tuple{Int64, Int64}, true, ModelingToolkitBase.MTKParameters{Array{Float64, 1}, Array{Float64, 1}, Tuple{}, Tuple{}, Tuple{}, Tuple{}}, SciMLBase.ODEFunction{true, SciMLBase.FullSpecialize, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x9286608c, 0xbd422303, 0x5105814a, 0xb02a1516, 0xa7001fd3), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x2e5e0cc9, 0x8e977946, 0x85221830, 0xe7d7fc02, 0x170cee2f), Nothing}}, LinearAlgebra.UniformScaling{Bool}, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, ModelingToolkitBase.ObservedFunctionCache{ModelingToolkitBase.System, Nothing}, Nothing, ModelingToolkitBase.System, SciMLBase.OverrideInitData{SciMLBase.NonlinearProblem{Nothing, true, ModelingToolkitBase.MTKParameters{Array{Float64, 1}, StaticArraysCore.SArray{Tuple{0}, Float64, 1, 0}, Tuple{}, Tuple{}, Tuple{}, Tuple{}}, SciMLBase.NonlinearFunction{true, SciMLBase.FullSpecialize, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xea2adeae, 0xdd074767, 0x3d747877, 0x201a9f0c, 0x0aa4b45c), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x3d86c3f8, 0x8cb34fec, 0xe037f03b, 0xf83be1ef, 0xde7515e1), Nothing}}, LinearAlgebra.UniformScaling{Bool}, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, ModelingToolkitBase.ObservedFunctionCache{ModelingToolkitBase.System, Nothing}, Nothing, ModelingToolkitBase.System, Nothing, Nothing}, Base.Pairs{Symbol, Union{}, Tuple{}, NamedTuple{(), Tuple{}}}, SciMLBase.StandardNonlinearProblem, Nothing, Nothing}, typeof(ModelingToolkitBase.update_initializeprob!), Base.ComposedFunction{Base.ComposedFunction{typeof(Base.identity), typeof(ModelingToolkitBase.safe_float)}, SymbolicIndexingInterface.TimeIndependentObservedFunction{ModelingToolkitBase.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xee8d4739, 0x1ca06c92, 0x85e813d6, 0x8a4a39d1, 0x4151a370), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xc7e3524e, 0xba2eb296, 0x5a2249fe, 0x4aa94222, 0x59c2d215), Nothing}}}}, ModelingToolkitBase.var"#initprobpmap_split#724"{ModelingToolkitBase.var"#_getter#720"{Tuple{Base.ComposedFunction{ModelingToolkitBase.PConstructorApplicator{typeof(Base.identity)}, ModelingToolkitBase.ObservedWrapper{false, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xb4d5953c, 0x14b4fe81, 0x865f6123, 0xcdae70a1, 0x8a920745), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x5a0161f5, 0x0f1d38ae, 0x61e3cb5a, 0xcc8bd82d, 0xd2e6676d), Nothing}}}}, Base.ComposedFunction{ModelingToolkitBase.PConstructorApplicator{typeof(Base.identity)}, ModelingToolkitBase.ObservedWrapper{false, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x22566f93, 0xab23bab3, 0x38ef30c8, 0xcf441c87, 0xcb86ec35), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xf515ee68, 0x9b29b354, 0xe5f11990, 0xaecc6ec8, 0x2f59ebe5), Nothing}}}}, Base.Returns{Tuple{}}, Base.ComposedFunction{Base.Fix1{typeof(Base.Broadcast.broadcast), ModelingToolkitBase.PConstructorApplicator{typeof(Base.identity)}}, ModelingToolkitBase.ObservedWrapper{false, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x48e1dbff, 0x79659666, 0x247b7c0c, 0x74a21739, 0x061a95cf), Nothing}, Nothing}}}, Base.ComposedFunction{Base.ComposedFunction{Base.Fix1{typeof(Base.Broadcast.broadcast), typeof(Base.identity)}, Base.Fix1{Base.Broadcast.BroadcastFunction{typeof(ModelingToolkitBase.call)}, Tuple{}}}, ModelingToolkitBase.ObservedWrapper{false, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x48e1dbff, 0x79659666, 0x247b7c0c, 0x74a21739, 0x061a95cf), Nothing}, Nothing}}}}}}, ModelingToolkitBase.InitializationMetadata{ModelingToolkitBase.ReconstructInitializeprob{ModelingToolkitBase.var"#_getter#720"{Tuple{Base.ComposedFunction{ModelingToolkitBase.PConstructorApplicator{typeof(Base.identity)}, ModelingToolkitBase.ObservedWrapper{true, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xb80930bc, 0x4260a78a, 0x379dc65c, 0x36796f11, 0xc57bcd0e), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x84e2a49f, 0x3f634732, 0x3e3c8d10, 0x8c840230, 0x1dce5821), Nothing}}}}, Base.Returns{StaticArraysCore.SArray{Tuple{0}, Float64, 1, 0}}, Base.Returns{Tuple{}}, Base.ComposedFunction{Base.Fix1{typeof(Base.Broadcast.broadcast), ModelingToolkitBase.PConstructorApplicator{typeof(Base.identity)}}, ModelingToolkitBase.ObservedWrapper{true, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xc0224667, 0x9004e642, 0x7c32774c, 0xb06209e5, 0x97152e08), Nothing}, Nothing}}}, Base.ComposedFunction{Base.ComposedFunction{Base.Fix1{typeof(Base.Broadcast.broadcast), typeof(Base.identity)}, Base.Fix1{Base.Broadcast.BroadcastFunction{typeof(ModelingToolkitBase.call)}, Tuple{}}}, ModelingToolkitBase.ObservedWrapper{true, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xc0224667, 0x9004e642, 0x7c32774c, 0xb06209e5, 0x97152e08), Nothing}, Nothing}}}}}, Base.ComposedFunction{typeof(Base.identity), ModelingToolkitBase.ObservedWrapper{true, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x890c50cf, 0xf615c474, 0xf66b0b5a, 0xbd4f7816, 0x011c2e85), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xa9c78342, 0x78ca9315, 0xb8f9f851, 0x2ad3286d, 0x7e34e5e3), Nothing}}}}}, ModelingToolkitBase.GetUpdatedU0{SymbolicIndexingInterface.TimeIndependentObservedFunction{ModelingToolkitBase.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xe870e9b2, 0x5a3750d2, 0xc70838d3, 0x8d743208, 0x48aeb939), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x3e1c1569, 0xcfa9999e, 0x320c1624, 0xa9932029, 0x17f66ade), Nothing}}}, SymbolicIndexingInterface.MultipleParametersGetter{SymbolicIndexingInterface.IndexerNotTimeseries, Array{SymbolicIndexingInterface.GetParameterIndex{ModelingToolkitBase.ParameterIndex{SciMLStructures.Initials, Int64}}, 1}, Nothing}}, ModelingToolkitBase.SetInitialUnknowns{SymbolicIndexingInterface.MultipleSetters{Array{SymbolicIndexingInterface.ParameterHookWrapper{SymbolicIndexingInterface.SetParameterIndex{ModelingToolkitBase.ParameterIndex{SciMLStructures.Initials, Int64}}, SymbolicUtils.BasicSymbolicImpl.var"typeof(BasicSymbolicImpl)"{SymbolicUtils.SymReal}}, 1}}}}, Base.Val{true}}, Nothing}, Base.Pairs{Symbol, Union{}, Tuple{}, NamedTuple{(), Tuple{}}}, SciMLBase.StandardODEProblem}).
This might be caused by recursion over very long tuples or argument lists.

KenCarp47(; linsolve = nothing, nlsolve = OrdinaryDiffEqNonlinearSolve.NLNewton{Rational{Int64}, Rational{Int64}, Rational{Int64}, Nothing}(1//100, 10, 1//5, 1//5, false, true, nothing), precs = DEFAULT_PRECS, smooth_est = true, extrapolant = linear, controller = PI, autodiff = ADTypes.AutoForwardDiff(),)

Without isoproterenol

@unpack Istim = sys
callback = build_stim_callbacks(Istim, stimend; period=1* 1000ms, starttime=stimstart)
@time sol = solve(prob, alg; callback)

Internal error: stack overflow in type inference of kwcall(NamedTuple{(:callback,), Tuple{SciMLBase.CallbackSet{Tuple{}, Tuple{SciMLBase.DiscreteCallback{DiffEqCallbacks.PresetTimeFunction{Base.StepRange{Int64, Int64}, typeof(SciMLBase.INITIALIZE_DEFAULT), CaMKIIModel.var"#15#17"{Float64, Float64, Symbolics.Num}}, CaMKIIModel.var"#15#17"{Float64, Float64, Symbolics.Num}, DiffEqCallbacks.PresetTimeFunction{Base.StepRange{Int64, Int64}, typeof(SciMLBase.INITIALIZE_DEFAULT), CaMKIIModel.var"#15#17"{Float64, Float64, Symbolics.Num}}, typeof(SciMLBase.FINALIZE_DEFAULT), Nothing, Tuple{}}, SciMLBase.DiscreteCallback{DiffEqCallbacks.PresetTimeFunction{Base.StepRangeLen{Float64, Base.TwicePrecision{Float64}, Base.TwicePrecision{Float64}, Int64}, typeof(SciMLBase.INITIALIZE_DEFAULT), CaMKIIModel.var"#16#18"{Float64, Float64, Symbolics.Num}}, CaMKIIModel.var"#16#18"{Float64, Float64, Symbolics.Num}, DiffEqCallbacks.PresetTimeFunction{Base.StepRangeLen{Float64, Base.TwicePrecision{Float64}, Base.TwicePrecision{Float64}, Int64}, typeof(SciMLBase.INITIALIZE_DEFAULT), CaMKIIModel.var"#16#18"{Float64, Float64, Symbolics.Num}}, typeof(SciMLBase.FINALIZE_DEFAULT), Nothing, Tuple{}}}}}}, typeof(CommonSolve.solve), SciMLBase.ODEProblem{Array{Float64, 1}, Tuple{Int64, Int64}, true, ModelingToolkitBase.MTKParameters{Array{Float64, 1}, Array{Float64, 1}, Tuple{}, Tuple{}, Tuple{}, Tuple{}}, SciMLBase.ODEFunction{true, SciMLBase.FullSpecialize, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x9286608c, 0xbd422303, 0x5105814a, 0xb02a1516, 0xa7001fd3), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x2e5e0cc9, 0x8e977946, 0x85221830, 0xe7d7fc02, 0x170cee2f), Nothing}}, LinearAlgebra.UniformScaling{Bool}, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, ModelingToolkitBase.ObservedFunctionCache{ModelingToolkitBase.System, Nothing}, Nothing, ModelingToolkitBase.System, SciMLBase.OverrideInitData{SciMLBase.NonlinearProblem{Nothing, true, ModelingToolkitBase.MTKParameters{Array{Float64, 1}, StaticArraysCore.SArray{Tuple{0}, Float64, 1, 0}, Tuple{}, Tuple{}, Tuple{}, Tuple{}}, SciMLBase.NonlinearFunction{true, SciMLBase.FullSpecialize, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xea2adeae, 0xdd074767, 0x3d747877, 0x201a9f0c, 0x0aa4b45c), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x3d86c3f8, 0x8cb34fec, 0xe037f03b, 0xf83be1ef, 0xde7515e1), Nothing}}, LinearAlgebra.UniformScaling{Bool}, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, Nothing, ModelingToolkitBase.ObservedFunctionCache{ModelingToolkitBase.System, Nothing}, Nothing, ModelingToolkitBase.System, Nothing, Nothing}, Base.Pairs{Symbol, Union{}, Tuple{}, NamedTuple{(), Tuple{}}}, SciMLBase.StandardNonlinearProblem, Nothing, Nothing}, typeof(ModelingToolkitBase.update_initializeprob!), Base.ComposedFunction{Base.ComposedFunction{typeof(Base.identity), typeof(ModelingToolkitBase.safe_float)}, SymbolicIndexingInterface.TimeIndependentObservedFunction{ModelingToolkitBase.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xee8d4739, 0x1ca06c92, 0x85e813d6, 0x8a4a39d1, 0x4151a370), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xc7e3524e, 0xba2eb296, 0x5a2249fe, 0x4aa94222, 0x59c2d215), Nothing}}}}, ModelingToolkitBase.var"#initprobpmap_split#724"{ModelingToolkitBase.var"#_getter#720"{Tuple{Base.ComposedFunction{ModelingToolkitBase.PConstructorApplicator{typeof(Base.identity)}, ModelingToolkitBase.ObservedWrapper{false, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xb4d5953c, 0x14b4fe81, 0x865f6123, 0xcdae70a1, 0x8a920745), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x5a0161f5, 0x0f1d38ae, 0x61e3cb5a, 0xcc8bd82d, 0xd2e6676d), Nothing}}}}, Base.ComposedFunction{ModelingToolkitBase.PConstructorApplicator{typeof(Base.identity)}, ModelingToolkitBase.ObservedWrapper{false, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x22566f93, 0xab23bab3, 0x38ef30c8, 0xcf441c87, 0xcb86ec35), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xf515ee68, 0x9b29b354, 0xe5f11990, 0xaecc6ec8, 0x2f59ebe5), Nothing}}}}, Base.Returns{Tuple{}}, Base.ComposedFunction{Base.Fix1{typeof(Base.Broadcast.broadcast), ModelingToolkitBase.PConstructorApplicator{typeof(Base.identity)}}, ModelingToolkitBase.ObservedWrapper{false, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x48e1dbff, 0x79659666, 0x247b7c0c, 0x74a21739, 0x061a95cf), Nothing}, Nothing}}}, Base.ComposedFunction{Base.ComposedFunction{Base.Fix1{typeof(Base.Broadcast.broadcast), typeof(Base.identity)}, Base.Fix1{Base.Broadcast.BroadcastFunction{typeof(ModelingToolkitBase.call)}, Tuple{}}}, ModelingToolkitBase.ObservedWrapper{false, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x48e1dbff, 0x79659666, 0x247b7c0c, 0x74a21739, 0x061a95cf), Nothing}, Nothing}}}}}}, ModelingToolkitBase.InitializationMetadata{ModelingToolkitBase.ReconstructInitializeprob{ModelingToolkitBase.var"#_getter#720"{Tuple{Base.ComposedFunction{ModelingToolkitBase.PConstructorApplicator{typeof(Base.identity)}, ModelingToolkitBase.ObservedWrapper{true, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xb80930bc, 0x4260a78a, 0x379dc65c, 0x36796f11, 0xc57bcd0e), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x84e2a49f, 0x3f634732, 0x3e3c8d10, 0x8c840230, 0x1dce5821), Nothing}}}}, Base.Returns{StaticArraysCore.SArray{Tuple{0}, Float64, 1, 0}}, Base.Returns{Tuple{}}, Base.ComposedFunction{Base.Fix1{typeof(Base.Broadcast.broadcast), ModelingToolkitBase.PConstructorApplicator{typeof(Base.identity)}}, ModelingToolkitBase.ObservedWrapper{true, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xc0224667, 0x9004e642, 0x7c32774c, 0xb06209e5, 0x97152e08), Nothing}, Nothing}}}, Base.ComposedFunction{Base.ComposedFunction{Base.Fix1{typeof(Base.Broadcast.broadcast), typeof(Base.identity)}, Base.Fix1{Base.Broadcast.BroadcastFunction{typeof(ModelingToolkitBase.call)}, Tuple{}}}, ModelingToolkitBase.ObservedWrapper{true, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xc0224667, 0x9004e642, 0x7c32774c, 0xb06209e5, 0x97152e08), Nothing}, Nothing}}}}}, Base.ComposedFunction{typeof(Base.identity), ModelingToolkitBase.ObservedWrapper{true, ModelingToolkitBase.GeneratedFunctionWrapper{(2, 3, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x890c50cf, 0xf615c474, 0xf66b0b5a, 0xbd4f7816, 0x011c2e85), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___, :t), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xa9c78342, 0x78ca9315, 0xb8f9f851, 0x2ad3286d, 0x7e34e5e3), Nothing}}}}}, ModelingToolkitBase.GetUpdatedU0{SymbolicIndexingInterface.TimeIndependentObservedFunction{ModelingToolkitBase.GeneratedFunctionWrapper{(2, 2, true), RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0xe870e9b2, 0x5a3750d2, 0xc70838d3, 0x8d743208, 0x48aeb939), Nothing}, RuntimeGeneratedFunctions.RuntimeGeneratedFunction{(:ˍ₋out, :__mtk_arg_1, :___mtkparameters___), ModelingToolkitBase.var"#_RGF_ModTag", ModelingToolkitBase.var"#_RGF_ModTag", (0x3e1c1569, 0xcfa9999e, 0x320c1624, 0xa9932029, 0x17f66ade), Nothing}}}, SymbolicIndexingInterface.MultipleParametersGetter{SymbolicIndexingInterface.IndexerNotTimeseries, Array{SymbolicIndexingInterface.GetParameterIndex{ModelingToolkitBase.ParameterIndex{SciMLStructures.Initials, Int64}}, 1}, Nothing}}, ModelingToolkitBase.SetInitialUnknowns{SymbolicIndexingInterface.MultipleSetters{Array{SymbolicIndexingInterface.ParameterHookWrapper{SymbolicIndexingInterface.SetParameterIndex{ModelingToolkitBase.ParameterIndex{SciMLStructures.Initials, Int64}}, SymbolicUtils.BasicSymbolicImpl.var"typeof(BasicSymbolicImpl)"{SymbolicUtils.SymReal}}, 1}}}}, Base.Val{true}}, Nothing}, Base.Pairs{Symbol, Union{}, Tuple{}, NamedTuple{(), Tuple{}}}, SciMLBase.StandardODEProblem}, OrdinaryDiffEqSDIRK.KenCarp47{0, ADTypes.AutoForwardDiff{nothing, Nothing}, Nothing, OrdinaryDiffEqNonlinearSolve.NLNewton{Base.Rational{Int64}, Base.Rational{Int64}, Base.Rational{Int64}, Nothing}, typeof(OrdinaryDiffEqCore.DEFAULT_PRECS), Base.Val{:forward}(), true, nothing}).
This might be caused by recursion over very long tuples or argument lists.
  6.745165 seconds (16.95 M allocations: 1.049 GiB, 3.06% gc time, 94.59% compilation time)

retcode: Success
Interpolation: 3rd order Hermite
t: 4020-element Vector{Float64}:
      0.0
      0.019333125036189135
      0.09098129266634847
      0.2073558192440938
      0.45611905918185225
      1.0472561699066012
      2.034266647380669
      3.451776427609829
      6.733791989961038
     12.450116263175316
      ⋮
 153105.79419874662
 157632.10459082667
 163094.44413596718
 168819.3462643782
 175121.3404167099
 182484.30738605672
 189876.83225674296
 197903.87397558178
 205000.0
u: 4020-element Vector{Vector{Float64}}:
 [830.0, 830.0, 0.0026, 0.07192, 0.07831, 0.26081, 0.00977, 0.00188, 0.09243, 0.22156  …  0.12113, 0.12113, 0.12113, 0.12113, 0.12113, 0.12113, 0.12113, 150952.75035000002, 13838.37602, -68.79268]
 [829.9999654017552, 829.9994975880237, 0.002598565958899963, 0.07192100954861869, 0.0783084540750169, 0.2608055799108062, 0.009769882842059355, 0.001879826176063952, 0.09242766669597557, 0.22156399388113623  …  0.12113000000933162, 0.12113000025734089, 0.1211300057338325, 0.12113010297093836, 0.12113142530654214, 0.12114821590793043, 0.121143876225781, 150952.7504077194, 13838.375711519522, -68.79732946230298]
 [829.9998348635114, 829.9976422525888, 0.0025933105248854755, 0.07192476229550161, 0.07830250341047809, 0.26078941009444856, 0.009769459049748559, 0.0018789042446954408, 0.09241901973935228, 0.22157879451042628  …  0.12113003148419571, 0.12113019157425117, 0.1211310080003016, 0.12113449709234102, 0.12114659468704474, 0.12119534717224295, 0.12117935237210484, 150952.75062244057, 13838.374513299239, -68.81607005191516]
 [829.9996133960518, 829.994650615981, 0.0025849478342343003, 0.07193089713739982, 0.07829207699960301, 0.26076387070239837, 0.009768805322611648, 0.0018766436939500898, 0.0924049756352414, 0.2216028323583001  …  0.12113087741239345, 0.12113274990086023, 0.1211377421114302, 0.12114946366929272, 0.1211735129279145, 0.12124561066298667, 0.12121643174100435, 150952.75097402377, 13838.372555328504, -68.84681913016406]
 [829.9990964775621, 829.988344553044, 0.0025677078039993283, 0.07194417536046811, 0.0782666763083778, 0.26071223836757207, 0.009767542947102269, 0.0018699196276109342, 0.09237495783324366, 0.22165420751509649  …  0.12113852905071927, 0.121146799702154, 0.12116114282208083, 0.12118436554344811, 0.12121949726910079, 0.12131904071172774, 0.12126925045394375, 150952.75173733698, 13838.368384399799, -68.91207315641022]
 [829.9976227532394, 829.9738229183572, 0.0025298083788575705, 0.0719766279718259, 0.07818995396102801, 0.2606050783338445, 0.009765228548992247, 0.0018505337735948656, 0.09230364341434424, 0.22177624782601593  …  0.12117136690641132, 0.12119087791259216, 0.12121719028561129, 0.1212516246654559, 0.1212953927432663, 0.1214343677642216, 0.12134948181642351, 150952.7536153353, 13838.35855929409, -69.06429957869561]
 [829.9944193672545, 829.9509077882478, 0.002474807984255052, 0.072033638008222, 0.07801428142318334, 0.2604711491247151, 0.00976340307695454, 0.0018178174457210696, 0.09218462778413179, 0.2219798988931877  …  0.12122865031168673, 0.12125703401370141, 0.1212913694284102, 0.1213322850700112, 0.1213803350357127, 0.12156232336183946, 0.12143597118898398, 150952.75694915676, 13838.342403295292, -69.31024282857501]
 [829.988353326151, 829.9205247588947, 0.002410689405003595, 0.07212165176212566, 0.07767036984052175, 0.260364872984163, 0.009765046552185823, 0.0017738156970858972, 0.09201383582103524, 0.22227216393618593  …  0.12129804817708402, 0.12133199175373688, 0.12137090293434043, 0.12141512691323042, 0.12146497038338351, 0.12168788172546924, 0.12152069323436775, 150952.7621562011, 13838.31972312405, -69.6463744385697]
 [829.9689941847354, 829.8589858081657, 0.0023106557375668943, 0.07235305493823077, 0.07655353014019994, 0.2604150766477604, 0.009786689195736801, 0.0016855899200154505, 0.09161908334733312, 0.22294828820039625  …  0.12141764334924618, 0.12145589096484646, 0.12149798567106192, 0.12154409799298801, 0.12159439029040946, 0.12186357098200122, 0.12164901526001325, 150952.775988694, 13838.26949390594, -70.35063780004249]
 [829.9235249884752, 829.7704141511887, 0.00222899504688523, 0.07284451721380114, 0.07399206775662617, 0.2610441779341529, 0.009873892897153878, 0.0015688569001333992, 0.0909342247513693, 0.22412560286423527  …  0.12157705626285502, 0.12161553145602244, 0.12165742958644533, 0.1217028608453571, 0.1217519421678341, 0.12200883559098283, 0.12180479776442218, 150952.805292636, 13838.188823477813, -71.35304497334121]
 ⋮
 [784.9060077281996, 784.5419653252194, 0.002043321057591016, 0.21514201907852049, 0.0003002959512006277, 0.0011149986926861795, 0.0015670088521856035, 0.0024256433807237493, 0.0015098982643737815, 0.9995947835650464  …  0.13696467264794546, 0.13696443498085373, 0.13696418511693775, 0.1369639225583901, 0.1369636467752689, 0.1369676442808164, 0.13696335720286404, 151183.0303652964, 13610.022044853049, -70.43523697223881]
 [784.9811487418223, 784.6212887493033, 0.002028026372705995, 0.21371059225456013, 0.00030366100030881124, 0.0011241658532123932, 0.0015731426118923701, 0.0024351310503810558, 0.0015214216405958021, 0.9997003621130545  …  0.13667312211139118, 0.13667321955354378, 0.1366733145459345, 0.13667340706198386, 0.13667349707338936, 0.1366677625453851, 0.13667358454998424, 151210.7407294698, 13582.339551782692, -70.38271133168625]
 [784.7531673045863, 784.399209328841, 0.002000143292065726, 0.21207966666571418, 0.0003075849826807969, 0.0011348310949804465, 0.0015802626138783464, 0.002446145706881385, 0.0015348071229416055, 0.9997327295290751  …  0.13628781187187372, 0.13628809810883427, 0.13628838748684563, 0.13628868024800014, 0.13628897665000722, 0.1362778133325685, 0.13628927696747356, 151243.4325274545, 13549.711394181091, -70.3219860003544]
 [784.3454755370938, 783.9980020458883, 0.0019667458631056063, 0.21044223043489968, 0.00031160624275764046, 0.0011457341595324003, 0.0015875213114296197, 0.0024573757375320033, 0.001548485941773714, 0.9997378185406957  …  0.1358739836649503, 0.13587435285216537, 0.1358747277481971, 0.13587510871674088, 0.135875496144958, 0.13586200814098226, 0.13587589044539822, 151276.83898163814, 13516.386701209023, -70.26035184767552]
 [783.815789432225, 783.475411670269, 0.0019289532739570142, 0.20870003316819016, 0.0003159793214516484, 0.0011575026998680697, 0.001595342031648493, 0.002469480037663435, 0.0015632814261005888, 0.9997359908327585  …  0.13542315279718095, 0.1354235568841906, 0.13542396788539732, 0.13542438621961947, 0.13542481233269782, 0.13541041440759075, 0.1354252466997105, 151312.62662085786, 13480.695265457156, -70.19422990667515]
 [783.1593388882692, 782.8269825655836, 0.0018856075869788137, 0.20672944950908245, 0.00032106883646297363, 0.001171118959265373, 0.0016043017711676196, 0.002483346572400953, 0.0015803057678607357, 0.9997320099848938  …  0.1349116867236799, 0.13491210245086402, 0.13491252565384426, 0.13491295677487572, 0.13491339628474733, 0.13489878191455673, 0.13491384468512296, 151353.168648772, 13440.267111404284, -70.11887157053683]
 [782.4907292664664, 782.1660577619382, 0.0018438347010227125, 0.20481373384829976, 0.0003261567006819331, 0.0011846224592959767, 0.0016131219685810532, 0.002496999416572009, 0.0015971501680948257, 0.9997277178726369  …  0.13441799407022836, 0.1344184099834115, 0.134418833595773, 0.13441926535673934, 0.13441970574473258, 0.13440520482180243, 0.13442015526955142, 151392.53962341367, 13401.009119123828, -70.04507729461032]
 [781.7678388399291, 781.4510794932797, 0.0018007052849973032, 0.20280036393188286, 0.0003315219709453885, 0.0011990239150064853, 0.0016225190998050874, 0.0025115360514171427, 0.001615172045809902, 0.9997230495082309  …  0.13390499414630763, 0.1339054055458898, 0.1339058247345633, 0.13390625216238267, 0.13390668830843921, 0.13389243918438737, 0.13390713368324147, 151433.82819449092, 13359.840452920365, -69.96695314811387]
 [781.1360723769301, 780.8259455783984, 0.0017645053340571688, 0.20107609725618367, 0.0003362456092241465, 0.0012115251617100988, 0.0016306590328041112, 0.0025241360830704253, 0.0016308711891527936, 0.9997189539610539  …  0.1334710319161622, 0.13347143772276043, 0.1334718513457767, 0.1334722732333902, 0.1334727038626966, 0.13345872097484032, 0.13347314374207775, 151469.1038717779, 13324.66803335805, -69.8995939732749]

i = (sys.t / 1000, sys.vm)
plot(sol, idxs=i, tspan=(100* 1000ms, 101* 1000ms), title="Action potential", xlabel="Time (s)")

plot(sol, idxs=(sys.t / 1000, [sys.Cai_sub_SR, sys.Cai_sub_SL, sys.Cai_mean]), tspan=(100* 1000ms, 101* 1000ms), title="Calcium transient", xlabel="Time (s)", ylabel="Conc. (μM)", label=["Ca (SR)" "Ca (SL)" "Ca (avg)"])

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

0.1uM isoproterenol

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

retcode: Success
Interpolation: 3rd order Hermite
t: 4133-element Vector{Float64}:
      0.0
      0.019332212642321225
      0.0909753536677785
      0.20734341371184017
      0.45612009091376227
      1.054995357790029
      2.0687582273987055
      3.532426469434026
      6.954474312708886
     12.881140394583184
      ⋮
 156343.49355685507
 161577.9110498221
 167076.33861167383
 173545.2310017575
 180014.12339184116
 187606.37557928413
 193771.13689269198
 202258.33455121622
 205000.0
u: 4133-element Vector{Vector{Float64}}:
 [830.0, 830.0, 0.0026, 0.07192, 0.07831, 0.26081, 0.00977, 0.00188, 0.09243, 0.22156  …  0.12113, 0.12113, 0.12113, 0.12113, 0.12113, 0.12113, 0.12113, 150952.75035000002, 13838.37602, -68.79268]
 [830.0014907813446, 829.9994983969315, 0.0025985617762304273, 0.07192100944210399, 0.0783084553009684, 0.26080557902518264, 0.009769882789156106, 0.0018798283012408296, 0.09242766680765373, 0.22156399369489554  …  0.12112999999292522, 0.12112999976760296, 0.12112999387241974, 0.12112987024898121, 0.12112789062781619, 0.12114085166973264, 0.12110606652224669, 150952.75040560117, 13838.375754627648, -68.79688468340858]
 [830.0069923284667, 829.9976597570311, 0.0025932333901093124, 0.07192476067836322, 0.07830252938628655, 0.2607893872547523, 0.009769457815684904, 0.0018789474207481205, 0.09241902049062925, 0.22157879333276254  …  0.12112997141448009, 0.12112979724154312, 0.12112876428747708, 0.12112366653491549, 0.12110348498933385, 0.12116995965002537, 0.12104232505356621, 150952.75061240068, 13838.374716347904, -68.81397720652195]
 [830.0158577078557, 829.9947407319254, 0.002584621445020041, 0.07193088967723144, 0.07829221002443341, 0.26076374828517723, 0.009768798977582772, 0.0018768406234711385, 0.09240497731107053, 0.22160283004626327  …  0.12112904116150658, 0.12112659359689947, 0.12111923336974709, 0.12109998399916658, 0.12105671234751013, 0.1212015065898643, 0.1209738344767147, 150952.75095089732, 13838.37301877309, -68.84205163854553]
 [830.0345419641031, 829.9887756071936, 0.002566503084444603, 0.07194414226033588, 0.0782673099528298, 0.26071163726429686, 0.009767513260543176, 0.001870661518018159, 0.09237495856789656, 0.22165420889035112  …  0.1211186772398533, 0.12110574303027867, 0.12108154537921717, 0.12103974679395182, 0.12097306261647259, 0.1212472872625492, 0.12087462901043557, 150952.7516853768, 13838.369406865308, -68.9016026006422]
 [830.0781441062189, 829.9758982036294, 0.002524878610254863, 0.07197688096026963, 0.07819213602269376, 0.2606006581173271, 0.009765055026764873, 0.0018527422062104577, 0.09230271444689127, 0.22177785080546492  …  0.12106523708621761, 0.12103027221783685, 0.1209812425602845, 0.1209148599010206, 0.12082798471552386, 0.12131789811020229, 0.12071794164123961, 150952.75351372664, 13838.360815588747, -69.04211843059183]
 [830.1479503090231, 829.9585434173905, 0.00246109995487889, 0.07203498340662612, 0.07801958620357542, 0.2604556542848459, 0.009762833375143309, 0.0018222096841450956, 0.09218048697196196, 0.22198703095477182  …  0.12096049453275325, 0.12090563619977981, 0.12083766561017403, 0.12075487994197644, 0.12065570846775478, 0.12139171591754938, 0.12053878864848538, 150952.75679928574, 13838.346581406078, -69.27157625798793]
 [830.2409658846126, 829.94224389674, 0.0023827586693918254, 0.07212474398358995, 0.07768264124671939, 0.260328819232537, 0.009763716677479951, 0.0017811002330017486, 0.09200417111776123, 0.22228882458514942  …  0.12082322914727563, 0.12075393967312678, 0.12067308427469069, 0.12057962941859937, 0.12047260650905556, 0.1214549734009331, 0.12035113491837604, 150952.7619496627, 13838.326681496434, -69.58534394428003]
 [830.429866475252, 829.9364424549942, 0.002249831523710559, 0.0723611819342855, 0.07658707307797623, 0.260316653230511, 0.009783000862600253, 0.0016985405235817768, 0.09159274690478587, 0.22299376443979835  …  0.12056534962083232, 0.12048046713091827, 0.1203860763569948, 0.12028157040392377, 0.12016635982381554, 0.12151237877680023, 0.12003987720811952, 150952.77573103562, 13838.28299428538, -70.2425025041705]
 [830.6928613603976, 829.9982399721617, 0.0021239182917267988, 0.07285328221842624, 0.07412597179118918, 0.2607890677408624, 0.009862701807495952, 0.0015916044882316508, 0.09088324179309899, 0.22421393891482522  …  0.12024287285952, 0.12014593800186038, 0.12004132076442421, 0.11992860889188607, 0.11980739182682856, 0.12147720561504817, 0.11967726150482463, 150952.80458617624, 13838.215505644463, -71.15507010102979]
 ⋮
 [922.9710762203831, 921.4607001074186, 0.0072382284607915215, 0.2180119657122698, 0.00029364415652703, 0.0010967795454824164, 0.001554718378175166, 0.0024066315786276044, 0.001486983273528492, 0.9996909543698603  …  0.12652038247687122, 0.12652028770108237, 0.12652018077536425, 0.12652006126460338, 0.1265199287056062, 0.12651758474393354, 0.12651978260479715, 150956.6187397962, 13826.3139940253, -70.54110239620816]
 [923.132380858799, 921.6415965057648, 0.0071430861105386215, 0.21619874493999022, 0.00029783262158074655, 0.001108216741416868, 0.0015625100267348854, 0.0024186931786154245, 0.0015014376455754006, 0.9997360964911328  …  0.12603561257393753, 0.12603552567387868, 0.1260354271492667, 0.12603531658584913, 0.12603519354265197, 0.12603278052271216, 0.1260350575497893, 150993.3248580379, 13789.661346526336, -70.47384313658003]
 [923.2897076841383, 921.8187762365221, 0.00704675836696542, 0.2143336693679071, 0.0003022640958461243, 0.0011202340895166139, 0.0015706131475269765, 0.002431236409581608, 0.0015165394760194408, 0.9997447685489426  …  0.1255431388896214, 0.12554305954347159, 0.12554296908959833, 0.12554286713401888, 0.12554275325734332, 0.125540281673859, 0.12554262701269306, 151030.95163019167, 13752.089575167036, -70.40424517555451]
 [923.4597983557275, 922.0113018460404, 0.006937998044506293, 0.21219057530308005, 0.0003074075847747631, 0.0011343094660256944, 0.0015800471885653634, 0.0024458301803550416, 0.001534195279305848, 0.9997434153264851  …  0.12498495044555342, 0.12498488013562824, 0.12498479933336612, 0.12498470766907656, 0.1249846047492263, 0.12498206052552875, 0.12498449015448518, 151074.03018787628, 13709.07420686321, -70.32372520443708]
 [923.6146796940502, 922.1876698259636, 0.006833932457242023, 0.21010169658960612, 0.00031256142350066525, 0.001148235198288518, 0.0015893577233938433, 0.0024602406299679843, 0.0015517253879033476, 0.9997395314411499  …  0.12444878585037689, 0.12444872361833517, 0.12444865145342511, 0.12444856900762256, 0.12444847591045394, 0.1244458736212719, 0.124448371767156, 151115.85868516465, 13667.307278800683, -70.24467637813238]
 [923.7784745419882, 922.375533612253, 0.006717473706651865, 0.20771755299692726, 0.00031860748773519733, 0.0011644920080408042, 0.0016001338142015537, 0.0024769184855299134, 0.0015721278118550552, 0.9997344348777522  …  0.12384625728935732, 0.12384620380246736, 0.12384614100922255, 0.12384606858590255, 0.12384598618790585, 0.12384333151767289, 0.12384589344803794, 151163.40772828346, 13619.82847885869, -70.15375875276028]
 [923.8981179677049, 922.5138459572912, 0.006627223111424011, 0.20583417577195576, 0.0003235037199064923, 0.001177599046651939, 0.001608762189443281, 0.0024902722237190415, 0.0015885558079317575, 0.9997302317215414  …  0.12337747592154578, 0.12337742895343418, 0.12337737315238018, 0.12337730821297939, 0.12337723381012773, 0.12337454361127122, 0.12337714959740674, 151200.82504223773, 13582.466611909424, -70.08139720437858]
 [924.044927612317, 922.685143150072, 0.0065089526722929315, 0.20331641291198327, 0.0003302196782819278, 0.0011954948266503416, 0.0016204575220125697, 0.0025083725356991114, 0.0016109541884254393, 0.9997244453889519  …  0.1227606058000186, 0.12276056721178016, 0.12276052040877414, 0.12276046510933547, 0.12276040101362927, 0.12275767094190546, 0.12276032780216135, 151250.65072358417, 13532.714966525467, -69.9839068001563]
 [924.0881177486593, 922.7359573679743, 0.006472153335978853, 0.20252122859744856, 0.0003323825181707364, 0.0012012353259204243, 0.0016241919072991693, 0.0025141527141680164, 0.0016181363872312432, 0.9997225814704304  …  0.12256809153386294, 0.12256805537123436, 0.12256801118381828, 0.12256795869725358, 0.12256789761947902, 0.12256516145958049, 0.12256782763928258, 151266.33949676596, 13517.04956495399, -69.95293149760676]

plot(sol2, idxs=(sys.t / 1000, sys.vm), tspan=(100* 1000ms, 101* 1000ms), title="Action potential", xlabel="Time (s)")

plot(sol2, idxs=(sys.t / 1000, [sys.Cai_sub_SR, sys.Cai_sub_SL, sys.Cai_mean]), tspan=(100* 1000ms, 101* 1000ms), title="Calcium transcient", xlabel="Time (s)", ylabel="Conc. (μM)", label=["Ca (SR)" "Ca (SL)" "Ca (avg)"])

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

Comparison

i = (sys.t / 1000, sys.Cai_mean)
tspan = (100* 1000ms, 101* 1000ms)
plot(sol, idxs=i, title="Calcium transcient", lab="ISO (-)"; tspan)
plot!(sol2, idxs=i, lab="ISO (0.1uM)", xlabel="Time (s)", ylabel="Concentration (μM)"; tspan)

savefig("iso-caT.pdf")

"/home/github/actions-runner-1/_work/camkii-cardiomyocyte-model/camkii-cardiomyocyte-model/docs/iso-caT.pdf"

Maximal and minimal calcium concentrations in calcium transients.

ca_ctl = sol(tspan[1]:1:tspan[2], idxs=sys.Cai_mean)
println(extrema(ca_ctl))

(0.2350435024166993, 0.578112961918151)

ca_iso = sol2(tspan[1]:1:tspan[2], idxs=sys.Cai_mean)
println(extrema(ca_iso))

(0.19033625819528058, 0.7110939142992273)

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

savefig("iso-camkact.pdf")

"/home/github/actions-runner-1/_work/camkii-cardiomyocyte-model/camkii-cardiomyocyte-model/docs/iso-camkact.pdf"

i = (sys.t / 1000, sys.vm)
tspan = (100* 1000ms, 101* 1000ms)
plot(sol, idxs=i, title="Action potential", lab="ISO (-)"; tspan)
plot!(sol2, idxs=i, lab="ISO (0.1uM)", xlabel="Time (ms)", ylabel="Voltage (mV)"; tspan)

Experimental data

chemicaldf = CSV.read(joinpath(@__DIR__, "data/CaMKAR-chemical.csv"), DataFrame)
ts = Dates.value.(chemicaldf[!, "Time"]) ./ 10^9
ctl = chemicaldf[!, "Ctrl Mean"]
ctl_error = chemicaldf[!, "Ctrl SD"] ./ sqrt.(chemicaldf[!, "Ctrl N"])

42-element Vector{Float64}:
 0.02305850621757014
 0.023225557529411765
 0.023536003837902393
 0.022995786588235295
 0.023056161133316953
 0.02236794743822152
 0.02448575734900888
 0.02631837493460871
 0.029628792824062226
 0.0306227531696316
 ⋮
 0.02665056333747046
 0.02525893438851731
 0.024749347823716496
 0.024158682609370527
 0.023572491294117648
 0.0240760416039372
 0.023230166
 0.023759599761907887
 0.02369791084482974

iso = chemicaldf[!, "isoproterenol 100nM Mean"]
iso_error = chemicaldf[!, "isoproterenol 100nM SD"] ./ sqrt.(chemicaldf[!, "isoproterenol 100nM N"])

42-element Vector{Float64}:
 0.01906411500114547
 0.019397124616823788
 0.019533446274478245
 0.019307032321568045
 0.0188119595
 0.019208707594448062
 0.020659484720981783
 0.022823236115241556
 0.02568418993766601
 0.02954342161034184
 ⋮
 0.022059148111952916
 0.020698453917127702
 0.020674867906488113
 0.019922601239830914
 0.019312468873824668
 0.019367967435545023
 0.018689615199686285
 0.01921783399052236
 0.01872515441384824

plot(ts, ctl, yerr=ctl_error, lab="Control", color=:blue, markerstrokecolor=:blue)
plot!(ts, iso, yerr=iso_error, lab="ISO 100nM", color=:red, markerstrokecolor=:red)
plot!(xlabel="Time (sec.)", ylabel="CaMKII activity (A.U.)")

savefig("iso-exp.pdf")

"/home/github/actions-runner-1/_work/camkii-cardiomyocyte-model/camkii-cardiomyocyte-model/docs/iso-exp.pdf"

Runtime information

using InteractiveUtils
InteractiveUtils.versioninfo()

Julia Version 1.10.10
Commit 95f30e51f41 (2025-06-27 09:51 UTC)
Build Info:
  Official https://julialang.org/ release
Platform Info:
  OS: Linux (x86_64-linux-gnu)
  CPU: 32 × Intel(R) Core(TM) i9-14900K
  WORD_SIZE: 64
  LIBM: libopenlibm
  LLVM: libLLVM-15.0.7 (ORCJIT, goldmont)
Threads: 2 default, 0 interactive, 1 GC (on 32 virtual cores)
Environment:
  JULIA_CONDAPKG_OFFLINE = true
  LD_LIBRARY_PATH = /home/github/actions-runner-1/_work/_tool/Python/3.14.3/x64/lib
  JULIA_PROJECT = /home/github/actions-runner-1/_work/camkii-cardiomyocyte-model/camkii-cardiomyocyte-model/Project.toml
  JULIA_CONDAPKG_BACKEND = Null
  JULIA_NUM_THREADS = 2
  JULIA_CI = true
  JULIA_DEPOT_PATH = /home/github/.julia:/home/github/actions-runner-1/_work/_tool/julia/1.10.10/x64/local/share/julia:/home/github/actions-runner-1/_work/_tool/julia/1.10.10/x64/share/julia
  JULIA_LOAD_PATH = @:@v#.#:@stdlib

using Pkg
Pkg.status()

Project CaMKIIModel v0.7.0
Status `~/actions-runner-1/_work/camkii-cardiomyocyte-model/camkii-cardiomyocyte-model/Project.toml`
  [336ed68f] CSV v0.10.16
⌃ [5a033b19] CurveFit v1.4.0
  [a93c6f00] DataFrames v1.8.1
  [459566f4] DiffEqCallbacks v4.12.0
  [f6369f11] ForwardDiff v1.3.2
  [682c06a0] JSON v1.4.0
  [23fbe1c1] Latexify v0.16.10
  [98b081ad] Literate v2.21.0
  [2fda8390] LsqFit v0.15.1
  [1862ce21] MarkdownTables v1.1.0
  [961ee093] ModelingToolkit v11.11.0
  [77ba4419] NaNMath v1.1.3
  [1dea7af3] OrdinaryDiffEq v6.108.0
  [91a5bcdd] Plots v1.41.6
  [0d7ed370] StaticArrayInterface v1.9.0
  [2913bbd2] StatsBase v0.34.10
  [9672c7b4] SteadyStateDiffEq v2.9.0
  [bd369af6] Tables v1.12.1
  [ea8e919c] SHA v0.7.0
Info Packages marked with ⌃ have new versions available and may be upgradable.

---

This notebook was generated using Literate.jl.