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 "cells": [
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "# Reaction Diffusion"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "In this example we consider a model where calcium ions interact with a buffer. We also add calcium extrusion."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "import sinaps as sn"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Initialization"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Creating a sample neuron:"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "nrn = sn.Neuron([(0,1),(1,2),(1,3),(3,4)])\n",
    "nrn.plot()"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Settings channels: note that the `Hodgkin_Huxley_Ca` channel needs to be added to account for calcium entry through voltage-gated calcium channels. The `Hodgkin_Huxley` channels only contains sodium, potassium and leak channels."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "nrn[0].clear_channels()#Reset all channels, useful if you re-run this cell (does nothing the first time)\n",
    "nrn[0].add_channel(sn.channels.PulseCurrent(500,2,3),0)\n",
    "nrn[0].add_channel(sn.channels.Hodgkin_Huxley())\n",
    "nrn[0].add_channel(sn.channels.Hodgkin_Huxley_Ca(gCa=14.5,V_Ca=115)) "
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "sim = sn.Simulation(nrn,dx=10)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "sim.run((0,100))"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "sim.plot()"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Chemical reactions"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Ion species can be added to the model via the function `add_species`"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "nrn.add_species(sn.Species.Ca)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Chemical reactions are defined with the reaction equation and the reaction\n",
    "rates:\n",
    "$$ Ca + Bf \\rightleftharpoons_{k_2}^{k_1} BfCa $$\n",
    "\n",
    "\n",
    "Reactions are simulated during the electrodiffusion simulation.\n",
    "\n",
    "Note that Species are automatically added to the neuron if they are not already\n",
    "present."
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#Reset reaction / not useful the first time\n",
    "nrn.reactions=[]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#shortcuts\n",
    "Ca=sn.Species.Ca\n",
    "BF=sn.Species.Buffer\n",
    "BFB=sn.Species.Buffer_Ca"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "nrn.add_reaction(\n",
    "    {Ca:1,\n",
    "     BF:1},\n",
    "    {BFB:1},\n",
    "    k1=0.2,\n",
    "    k2=0.1)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "The calcium extrusion is modeled using the equation:\n",
    "$$ Ca  \\rightleftharpoons^{k_1} \\emptyset $$"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#Calcium extrusion\n",
    "nrn.add_reaction(\n",
    "    {Ca:1},\n",
    "    {},\n",
    "    k1=0.05,k2=0)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "Initial concentrations can be set:"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "#Calcium initial concentration\n",
    "for s in nrn.sections:\n",
    "    s.C0[Ca]=10**(-4)\n",
    "    s.C0[BF]=2*10**(-3)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Running electro diffusion simulatiom"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "sim.run_diff(max_step=1)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## Plotting results"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "sim.plot.C(Ca)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "sim.plot.C(BFB)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "(sim.plot.V().opts(width=900,height=200) \n",
    " + sim.plot.C(Ca) .opts(width=900,height=200) \n",
    " + sim.plot.C(BFB).opts(width=900,height=200) \n",
    ").cols(1).opts(plot={'shared_axes':False})"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": [
    "sim.plot.C_field(Ca)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": null,
   "metadata": {},
   "outputs": [],
   "source": []
  }
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