: Authors: Ashhad S and Narayanan R, 2013 INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)} NEURON { POINT_PROCESS mGLUR RANGE G, C, lastrelease RANGE Cmax, Cdur, Deadtime, K1, K2, initmGluR USEION ip3 WRITE iip3 VALENCE 1 } UNITS { (mM) = (milli/liter) (uM)= (micro/liter) (mA) = (milliamp) } PARAMETER { initmGluR=0.3e-3 (mM): Bhalla & Iyenger Science 1999 Cmax = 1 (mM) : max transmitter concentration Deadtime = 1 (ms) : mimimum time between release events K1 = 0.28 (/ms uM) : forward binding rate to receptor from Bhalla et al K2 = 0.016 (/ms) : backward (unbinding) rate of receptor from Bhalla et al K_PLC = 5 (uM) :total concentration of PLC K_PIP2 = 160 (uM) :total concentration of PIP2 K_G=25 (uM) :kplc and Vmax describe aPLC catalyzing IP3 production from PIP2 kfplc = 0.83(/ms) kbplc = 0.68 (/ms) : 0.1/ms in the paper; added to Vmax1=0.58/ms in the paper Vmax1 = 0.58 (/ms) :D5 and D6 describe Glu_mGluR catalyzing G_alpha production, Km2=(D6f+D5B)/D5f D5f = 15 (/ms) D5b = 7.2 (/ms) D6f = 1.8(/ms) Vmax2 = 1.8 (/ms) Km2 = 0.6 (uM) :G2 describe aG binding to PLC G2f = 100 (/ms) G2b = 100 (/ms) :degradation of aG (D7f) and IP3 (G9f) D7f =9 (/ms) G9f = 0.75(/ms) :4 in original paper Cdur=2 (ms) : transmitter duration (rising phase) } ASSIGNED { C (mM) : transmitter concentration lastrelease (ms) : time of last spike iip3 (mA/cm2) } STATE { aG : fraction of activated G-protein aPLC_aG aPLC_PIP2 Glu_mGluR GG_mGluR ip3 degip3 mGluR PLC PIP2 G } INITIAL { Glu_mGluR = 0 GG_mGluR = 0 aPLC_aG=0 :0.0035 aPLC_PIP2=0 aG =0: 0.0007 iip3= 0 ip3= 0 G=K_G-(aG+GG_mGluR+aPLC_aG+aPLC_PIP2) PLC=K_PLC-(aPLC_aG+aPLC_PIP2) PIP2=K_PIP2-(aPLC_PIP2+ip3) mGluR=initmGluR lastrelease = -1e8 } BREAKPOINT { evaluateC() SOLVE bindkin METHOD sparse } KINETIC bindkin { ~ mGluR <-> Glu_mGluR (C*K1, K2) ~ Glu_mGluR + G <-> GG_mGluR (D5f,D5b) ~ GG_mGluR <-> aG+mGluR (D6f,0) ~ aG <-> G (D7f,0) ~ aG+PLC <-> aPLC_aG (G2f, G2b) ~ aPLC_aG+PIP2 <-> aPLC_PIP2 (kfplc,kbplc) ~ aPLC_PIP2 <-> ip3 (Vmax1,0) ~ ip3 <-> degip3 (G9f,0) :CONSERVE G+aG+GG_mGluR+aPLC_aG+aPLC_PIP2=K_G :CONSERVE PLC+aPLC_aG+aPLC_PIP2=K_PLC :CONSERVE PIP2+aPLC_PIP2+ip3=K_PIP2 iip3= ip3 } PROCEDURE evaluateC() { LOCAL q q = ((t - lastrelease) - Cdur) : time since last release ended if (q >= 0 && q <= Deadtime && C == Cmax) { : in dead time after release C = 0. } } NET_RECEIVE (weight (umho)) { LOCAL q q = ((t - lastrelease) - Cdur) : time since last release ended : Spike has arrived, ready for another release? if (q > Deadtime) { C = Cmax : start new release lastrelease = t } }