TITLE Q-type (not P) calcium channel for nucleus accumbens neuron : see comments at end of file UNITS { (mV) = (millivolt) (mA) = (milliamp) (S) = (siemens) (molar) = (1/liter) (mM) = (millimolar) FARADAY = (faraday) (coulomb) R = (k-mole) (joule/degC) } NEURON { SUFFIX caq USEION ca READ cai, cao WRITE ica RANGE pcaqbar, ica } PARAMETER { pcaqbar = 6.0e-6(cm/s) : vh = -100 mV, 120 ms pulse to 0 mV mvhalf = -9.0 (mV) : Churchill 1998, fig 5 mslope = -6.6 (mV) : Churchill 1998, fig 5 mtau = 1.13 (ms) : Randall 1995, fig 13 mshift = 0 (mV) qfact = 3 : m recorded at 22 C } ASSIGNED { v (mV) eca (mV) ica (mA/cm2) minf celsius (degC) cai (mM) cao (mM) } STATE { m } BREAKPOINT { SOLVE states METHOD cnexp ica = ghk(v,cai,cao) * pcaqbar * m * m : Kasai 92, Brown 93 } INITIAL { settables(v) m = minf } DERIVATIVE states { settables(v) m' = (minf - m) / (mtau/qfact) } PROCEDURE settables( v (mV) ) { TABLE minf DEPEND mshift FROM -100 TO 100 WITH 201 minf = 1 / ( 1 + exp( (v-mvhalf-mshift) / mslope) ) } :::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::: : ghk() borrowed from cachan.mod share file in Neuron FUNCTION ghk(v(mV), ci(mM), co(mM)) (.001 coul/cm3) { LOCAL z, eci, eco z = (1e-3)*2*FARADAY*v/(R*(celsius+273.15)) eco = co*efun(z) eci = ci*efun(-z) :high cao charge moves inward :negative potential charge moves inward ghk = (.001)*2*FARADAY*(eci - eco) } FUNCTION efun(z) { if (fabs(z) < 1e-4) { efun = 1 - z/2 }else{ efun = z/(exp(z) - 1) } } COMMENT Brown AM, Schwindt PC, Crill WE (1993) Voltage dependence and activation kinetics of pharmacologically defined components of the high-threshold calcium current in rat neocortical neurons. J Neurophysiol 70:1530-1543. Churchill D, Macvicar BA (1998) Biophysical and pharmacological characterization of voltage-dependent Ca2+ channels in neurons isolated from rat nucleus accumbens. J Neurophysiol 79:635-647. Kasai H, Neher E (1992) Dihydropyridine-sensitive and omega-conotoxin-sensitive calcium channels in a mammalian neuroblastoma-glioma cell line. J Physiol 448:161-188. Mermelstein PG, Foehring RC, Tkatch T, Song WJ, Baranauskas G, Surmeier DJ (1999) Properties of Q-type calcium channels in neostriatal and cortical neurons are correlated with beta subunit expression. J Neurosci 19:7268-7277. Randall A, Tsien RW (1995) Pharmacological dissection of multiple types of Ca2+ channel currents in rat cerebellar granule neurons. J Neurosci 15:2995-3012. Koch, C., and Segev, I., eds. (1998). Methods in Neuronal Modeling: From Ions to Networks, 2 edn (Cambridge, MA, MIT Press). Hille, B. (1992). Ionic Channels of Excitable Membranes, 2 edn (Sunderland, MA, Sinauer Associates Inc.). This is the w-agatoxin IVA (low conc (~20 nM) blocks P, high conc (~200 nM) blocks Q & P) sensitive current in fig 5 from Churchill - no P current. This current does not inactivate. Mermelstein 99 - very slow inactivation (2 s). Churchill 98 - small-to-no inactivating component - so ignore inactivation. The standard HH model uses a linear approximation to the driving force for an ion: (Vm - ez). This is ok for na and k, but not ca - calcium rectifies at high potentials because 1. internal and external concentrations of ca are so different, making outward current flow much more difficult than inward 2. calcium is divalent so rectification is more sudden than for na and k. (Hille 1992, pg 107) Accordingly, we need to replace the HH formulation with the GHK model, which accounts for this phenomenon. The GHK equation is eq 6.6 in Koch 1998, pg 217 - it expresses Ica in terms of Ca channel permeability (Perm,ca) times a mess. The mess can be circumvented using the ghk function below, which is included in the Neuron share files. Perm,ca can be expressed in an HH-like fashion as Perm,ca = pcabar * mca * mca (or however many m's and h's) where pcabar has dimensions of permeability but can be thought of as max conductance (Koch says it should be about 10^7 times smaller than the HH gbar - dont know) and mca is analagous to m (check out Koch 1998 pg 144) Calcium current can then be modeled as ica = pcabar * mca * mca * ghk() Jason Moyer 2004 - jtmoyer@seas.upenn.edu ENDCOMMENT