\documentclass{article} \usepackage{amsmath} \usepackage{xspace} \usepackage{mhchem} \usepackage[amssymb]{SIunits} \addunit{\molar}{M} \newcommand{\ICa}{\ensuremath{I_\mathrm{Ca}}\xspace} \newcommand{\gCa}{\ensuremath{g_\mathrm{Ca}}\xspace} \newcommand{\ECa}{\ensuremath{E_\mathrm{Ca}}\xspace} \newcommand{\Cmem}{\ensuremath{C_\mathrm{m}}\xspace} \newcommand{\dif}{\textrm{d}} \newcommand{\cCa}{[\textrm{Ca}]} \begin{document} \begin{table} \centering \begin{tabular}{lll} Quantity & Symbol & Units \\ \hline Voltage & $V$ & mV \\ Time & $t$ & ms \\ Conductance & $g$ & \siemens\per\centi\square\meter \\ Concentration & [Ca] & mM \\ Faraday const. & $F$ & C\per\mole \\ Length & $l$ & \micro\meter \\ Diameter & $d$ & \micro\meter \\ Capacitance & $\Cmem$ & \micro\farad\per\centi\square\meter \\ \hline \end{tabular} \caption{Quantities, symbols and units} \label{tab:quantities} \end{table} \clearpage \section{Test 1 - Ca accumulation} \label{tests:sec:test-1-ca} 1 compartment, length $L$, diameter $d$, membrane capacitance \Cmem, membrane potential $V$. Calcium current $\ICa=\gCa(V-\ECa)$, where $g$ is conductance and $\ECa$ is calcium reversal potential. $g$ is 0 apart from when it is set to $\overline{g}$ from $t_1$ to $t_2$. ODEs describing membrane potential and calcium concentration: \begin{equation} \label{tests:eq:1} \Cmem\frac{\dif V}{\dif t} = \ICa \end{equation} This can be solved: \begin{equation} \label{tests:eq:2} V(t) = V(t_0) + (\ECa - V(t_0))(1-\exp((t-t_0)\gCa/\Cmem)) \end{equation} The equation describing the calcium concentration [Ca] is: \begin{equation} \frac{\dif [\mathrm{Ca}]}{\dif t} = \frac{\ICa a }{2Fv} = \frac{2\ICa }{Fd} \end{equation} where $a= \pi Ld$ is the surface area and $v = \pi Ld^2/4$ is the volume. Hence following should be true: \begin{equation} [\textrm{Ca}](t_1) - [\textrm{Ca}](t_0) = \frac{\Cmem a (V(t_1) - V(t_0)) }{2Fv} = \frac{2\Cmem (V(t_1) - V(t_0)) }{Fd} \end{equation} Hence the factor-label method gives: \begin{equation} \begin{split} \frac{\micro\farad}{\centi\square\meter}\cdot\frac{\micro\meter\squared\cdot\milli\volt}% {\coulomb\per\mole\cdot\micro\meter\cubed} = \frac{10^{-6} \farad}{10^{-4}\square\meter}\cdot\frac{\mole\cdot10^{-3}\volt}% {\coulomb\cdot10^{-6}\meter} = \frac{10^{-6} \coulomb}{10^{-4}\volt\square\meter}\cdot\frac{\mole\cdot10^{-3}\volt}% {\coulomb\cdot10^{-6}\meter}\\ = \frac{10^1\mole}{\meter\cubed} = \frac{10^1\mole}{10^3\deci\meter\cubed} = 10^{-2}\molar = 10\milli\molar \end{split} \end{equation} \clearpage \section{Test 2 - Ca accumulation with linear pump} \label{tests:sec:test-1-ca} \begin{itemize} \item 1 compartment, length $L$, diameter $d$, membrane capacitance \Cmem, membrane potential $V$. \item Calcium channel current $\ICa^\mathrm{chan}=\gCa(V-\ECa)$, where $g$ is conductance and $\ECa$ is calcium reversal potential. \item Calcium pump current $\ICa^\mathrm{pump}=- \frac{Fdk_1}{2}\cCa$, where $k_1$ is a constant. \item $g$ is 0 apart from when it is set to $\overline{g}$ from $t_1$ to $t_2$. \end{itemize} ODEs describing membrane potential and calcium concentration: \begin{equation} \begin{split} \Cmem\frac{\dif V}{\dif t} = -\ICa^\mathrm{chan} - \ICa^\mathrm{pump} = \gCa(\ECa - V) - \frac{Fdk_1}{2}\cCa ) \\ \frac{\dif\cCa}{\dif t} = -\frac{2\ICa^\mathrm{chan}}{Fd} - k_1\cCa = \frac{2}{Fd} \left(\gCa(\ECa - V) - \frac{Fdk_1}{2}\cCa \right) \end{split} \end{equation} This can be solved: \begin{equation} \label{tests:eq:2} V(t) = V(t_0) + (V_\infty - V(t_0))(1-\exp((t-t_0)/\tau)) \end{equation} Where \begin{equation} \label{tests:eq:5} V_\infty = \frac{g\ECa + \Cmem k_1 V(t_0)}{g + \Cmem k_1} \quad \mbox{and} \quad \tau = \frac{\Cmem}{g + k_1\Cmem} \end{equation} For the dimensions of our quantities we need: \begin{equation} \label{tests:eq:5} V_\infty = \frac{10^3g\ECa + \Cmem k_1 V(t_0)}{10^3g + \Cmem k_1} \quad \mbox{and} \quad \tau = \frac{\Cmem}{10^3g + k_1\Cmem} \end{equation} \clearpage \section{Test 3 - Ca accumulation with nonlinear pump} \label{tests:sec:test-3-ca} \begin{itemize} \item 1 compartment, length $L$, diameter $d$, membrane capacitance \Cmem, membrane potential $V$. \item Calcium channel current $\ICa^\mathrm{chan}=\gCa(V-\ECa)$, where $g$ is conductance and $\ECa$ is calcium reversal potential. \item Pump is modelled using a pump molecule P with starting density $[\ce{P}]_0$ and pump reactions: \begin{equation} \label{tests:eq:3} \begin{aligned} \textrm{Ca binding:}\quad & \ce{P + Ca ->[k_1] P.Ca} \\ \textrm{Ca release:}\quad & \ce{P.Ca ->[k_2] P} \end{aligned} \end{equation} \item Thus the calcium pump current $\ICa^\mathrm{pump}=- \frac{Fdk_2}{2}[\ce{P.Ca}]$, where $k_1$ is a constant. \item $g$ is 0 apart from when it is set to $\overline{g}$ from $t_1$ to $t_2$. \end{itemize} ODEs describing membrane potential and calcium concentration: \begin{equation} \begin{aligned} \Cmem\frac{\dif V}{\dif t} & %= -\ICa^\mathrm{chan} - \ICa^\mathrm{pump} = \gCa(\ECa - V) - \frac{Fdk_2}{2}[\ce{P.Ca}] ) = \gCa(\ECa - V) - \frac{Fdk_2}{2}([\ce{P}]_0 - [\ce{P}] ) \\ \frac{\dif\cCa}{\dif t} & = -\frac{2\ICa^\mathrm{chan}}{Fd} - k_1[\ce{P}][\ce{Ca}] = \frac{2}{Fd} \left(\gCa(\ECa - V) - k_1[\ce{P}][\ce{Ca}] \right) \\ \frac{\dif[\ce{P}]}{\dif t} & = -k_1[\ce{P}][\ce{Ca}] + k_2[\ce{P.Ca}] = -k_1[\ce{P}][\ce{Ca}] + k_2([\ce{P}]_0 - [\ce{P}]) \end{aligned} \end{equation} This pump is nonlinear, even with fixed $E_{\mathrm{Ca}}$. Thus an analytical solution is harder, if not impossible. However, we can say the following: \begin{itemize} \item If $k_2=0$, Ca and voltage will rise during pulse, then voltage will remain steady, but Ca concentration will decline. \end{itemize} \end{document}