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model desc
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‎docs/iso-effects.ipynb‎

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{
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"cells": [
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{
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"cell_type": "markdown",
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"id": "03f46b26",
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"metadata": {},
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"source": [
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"# Effects of isoproterenol"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "186be4a6",
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"metadata": {},
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"outputs": [],
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"source": [
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"using ModelingToolkit\n",
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"using OrdinaryDiffEq, SteadyStateDiffEq, DiffEqCallbacks\n",
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"using Plots\n",
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"using CSV\n",
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"using DataFrames\n",
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"using Dates\n",
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"using CaMKIIModel\n",
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"using CaMKIIModel: second, μM\n",
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"Plots.default(lw=1.5)"
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]
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},
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{
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"cell_type": "markdown",
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"id": "1dbd36d1",
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"metadata": {},
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"source": [
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"## Setup model"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "508feb7c",
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"metadata": {},
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"outputs": [],
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"source": [
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"sys = build_neonatal_ecc_sys(simplify=true, reduce_iso=true, reduce_camk=true)\n",
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"tend = 205second\n",
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"prob = ODEProblem(sys, [], tend)\n",
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"stimstart = 30second\n",
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"stimend = 120second\n",
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"alg = KenCarp47()"
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]
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},
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{
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"cell_type": "markdown",
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"id": "133cdc7a",
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"metadata": {},
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"source": [
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"## Without isoproterenol"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "a7751eaf",
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"metadata": {},
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"outputs": [],
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"source": [
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"@unpack Istim = sys\n",
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"callback = build_stim_callbacks(Istim, stimend; period=1second, starttime=stimstart)\n",
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"@time sol = solve(prob, alg; callback)"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "177fbe83",
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"metadata": {},
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"outputs": [],
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"source": [
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"i = (sys.t / 1000, sys.vm)\n",
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"plot(sol, idxs=i, tspan=(100second, 101second), title=\"Action potential\", xlabel=\"Time (s)\")"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "84300558",
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"metadata": {},
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"outputs": [],
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"source": [
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"plot(sol, idxs=(sys.t / 1000, [sys.Cai_sub_SR, sys.Cai_sub_SL, sys.Cai_mean]), tspan=(100second, 101second), title=\"Calcium transient\", xlabel=\"Time (s)\", ylabel=\"Conc. (μM)\", label=[\"Ca (SR)\" \"Ca (SL)\" \"Ca (avg)\"])"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "3d16357b",
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"metadata": {},
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"outputs": [],
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"source": [
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"plot(sol, idxs=(sys.t / 1000, sys.CaMKAct * 100), title=\"Active CaMKII\", label=false, ylabel=\"Active fraction (%)\", xlabel=\"Time (s)\")"
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]
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},
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{
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"cell_type": "markdown",
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"id": "ec7e598d",
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"metadata": {},
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"source": [
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"## 0.1uM isoproterenol"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "fade2254",
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"metadata": {},
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"outputs": [],
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"source": [
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"prob2 = remake(prob, p=[sys.ISO => 0.1μM])\n",
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"sol2 = solve(prob2, alg; callback)"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "ae649703",
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"metadata": {},
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"outputs": [],
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"source": [
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"plot(sol2, idxs=(sys.t / 1000, sys.vm), tspan=(100second, 101second), title=\"Action potential\", xlabel=\"Time (s)\")"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "07f5a634",
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"metadata": {},
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"outputs": [],
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"source": [
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"plot(sol2, idxs=(sys.t / 1000, [sys.Cai_sub_SR, sys.Cai_sub_SL, sys.Cai_mean]), tspan=(100second, 101second), title=\"Calcium transcient\", xlabel=\"Time (s)\", ylabel=\"Conc. (μM)\", label=[\"Ca (SR)\" \"Ca (SL)\" \"Ca (avg)\"])"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "d7cbf5a2",
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"metadata": {},
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"outputs": [],
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"source": [
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"plot(sol2, idxs=(sys.t / 1000, sys.CaMKAct * 100), title=\"Active CaMKII\", label=false, ylabel=\"Active fraction (%)\", xlabel=\"Time (s)\")"
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]
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},
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{
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"cell_type": "markdown",
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"id": "f9025666",
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"metadata": {},
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"source": [
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"## Comparison"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "eb144dd3",
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"metadata": {},
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"outputs": [],
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"source": [
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"i = (sys.t / 1000, sys.Cai_mean)\n",
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"tspan = (100second, 101second)\n",
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"plot(sol, idxs=i, title=\"Calcium transcient\", lab=\"ISO (-)\"; tspan)\n",
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"plot!(sol2, idxs=i, lab=\"ISO (0.1uM)\", xlabel=\"Time (s)\", ylabel=\"Concentration (μM)\"; tspan)"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "5d73e22b",
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"metadata": {},
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"outputs": [],
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"source": [
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"savefig(\"iso-caT.pdf\")"
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]
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},
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{
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"cell_type": "markdown",
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"id": "d82a623e",
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"metadata": {},
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"source": [
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"Maximal and minimal calcium concentrations in calcium transients."
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "a867605f",
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"metadata": {},
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"outputs": [],
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"source": [
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"ca_ctl = sol(tspan[1]:1:tspan[2], idxs=sys.Cai_mean)\n",
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"println(extrema(ca_ctl))"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "331198b3",
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"metadata": {},
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"outputs": [],
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"source": [
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"ca_iso = sol2(tspan[1]:1:tspan[2], idxs=sys.Cai_mean)\n",
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"println(extrema(ca_iso))"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "31da0784",
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"metadata": {},
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"outputs": [],
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"source": [
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"i = (sys.t / 1000, sys.CaMKAct * 100)\n",
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"plot(sol, idxs=i, title=\"Active CaMKII\", lab=\"ISO (-)\")\n",
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"plot!(sol2, idxs=i, lab=\"ISO (0.1uM)\", ylabel=\"Active fraction (%)\", xlabel=\"Time (s)\")"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "765655b0",
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"metadata": {},
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"outputs": [],
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"source": [
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"savefig(\"iso-camkact.pdf\")"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "a4e81ca9",
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"metadata": {},
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"outputs": [],
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"source": [
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"i = (sys.t / 1000, sys.vm)\n",
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"tspan = (100second, 101second)\n",
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"plot(sol, idxs=i, title=\"Action potential\", lab=\"ISO (-)\"; tspan)\n",
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"plot!(sol2, idxs=i, lab=\"ISO (0.1uM)\", xlabel=\"Time (ms)\", ylabel=\"Voltage (mV)\"; tspan)"
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]
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},
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{
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"cell_type": "markdown",
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"id": "066cd384",
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"metadata": {},
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"source": [
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"## Experimental data"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "10748a73",
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"metadata": {},
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"outputs": [],
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"source": [
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"chemicaldf = CSV.read(joinpath(@__DIR__, \"data/CaMKAR-chemical.csv\"), DataFrame)\n",
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"ts = Dates.value.(chemicaldf[!, \"Time\"]) ./ 10^9\n",
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"ctl = chemicaldf[!, \"Ctrl Mean\"]\n",
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"ctl_error = chemicaldf[!, \"Ctrl SD\"] ./ sqrt.(chemicaldf[!, \"Ctrl N\"])"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "04073b8a",
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"metadata": {},
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"outputs": [],
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"source": [
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"iso = chemicaldf[!, \"isoproterenol 100nM Mean\"]\n",
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"iso_error = chemicaldf[!, \"isoproterenol 100nM SD\"] ./ sqrt.(chemicaldf[!, \"isoproterenol 100nM N\"])"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "5a02bb39",
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"metadata": {},
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"outputs": [],
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"source": [
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"plot(ts, ctl, yerr=ctl_error, lab=\"Control\", color=:blue, markerstrokecolor=:blue)\n",
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"plot!(ts, iso, yerr=iso_error, lab=\"ISO 100nM\", color=:red, markerstrokecolor=:red)\n",
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"plot!(xlabel=\"Time (sec.)\", ylabel=\"CaMKII activity (A.U.)\")\n"
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]
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},
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{
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"cell_type": "code",
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"execution_count": null,
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"id": "676c095e",
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"metadata": {},
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"outputs": [],
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"source": [
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"savefig(\"iso-exp.pdf\")"
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]
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}
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],
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"metadata": {
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"kernelspec": {
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"display_name": "Julia 1.12.2",
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"language": "julia",
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"name": "julia-1.12"
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},
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"language_info": {
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"file_extension": ".jl",
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"mimetype": "application/julia",
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"name": "julia",
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"version": "1.12.2"
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}
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},
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"nbformat": 4,
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"nbformat_minor": 5
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}

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