# Endo_16.ode # This XPPAUT file contains the program for the activity of a # pituitary corticotroph and the effects of CORT as described in # the paper "Glucocorticoids Inhibit CRH/AVP-Evoked Bursting Activity of # Male Murine Anterior Pituitary Corticotrophs", # Peter J. Duncan, Joel Tabak, Peter Ruth, Richard Bertram and # Michael J. Shipston, Endocrinology, 157:3108-3121, 2016. # Variables: # v -- membrane potential # n -- delayed rectifier activation variable # c -- free cytosolic calcium concentration # bf -- activation variable for BK-far channels # bn -- activation variable for BK-near channels # For figures in new paper: # # Note that gnscort will take different values in CRH/AVP vs. CRH. # With CRH/AVP use gnscort=0.15, and with CRH use gnscort=0.11 # Logical parameters are used to adjust everything else. # #initial conditions v(0)=-60 n(0)=0.1 c(0)=0.1 bf(0)=0.1 bn(0)=0.1 # Parameter values for different conditions: # Note that gnscort will take different values in CRH/AVP vs. CRH. # With CRH/AVP use gnscort=0.15, and with CRH use gnscort=0.11 # Logical parameters are used to adjust everything else. #Set CRH=1 for CRH (bursting) and CRH=0 for no CRH (spiking) #Set AVP=1 if AVP present, AVP=0 if not #Set KO=1 if BKKO, otherwise KO=0 #Set CORT=1 if CORT is present, otherwise CORT=0 par gnscort=0.15 par CRH=0,AVP=0,KO=0,CORT=0 # Other parameter values par sigmaN=5 par taubkf=2,taubkns=20,taubknb=2,gbknear=2,gbkfar=1 par gcals=1.8,gcalb=2.4,gir=1,gkdr=8.2,gnss=0.12,gnsavp=0.2 par Cm=6 par kcabkns=2,kcabknb=6 par vk=-75,sm=10,taun=40 par kcabkf=0.6,kbk=3 par A=0.12 num kc=0.12, ff=0.01 num vca=60,vir=-60 num vm=-20,vn=-5,sn=10 num alpha=0.0015 vns=-10 num sr=-1 num vbk0=0.1,kshift=18 # Functions gcal= gcals*(CRH*(gcalb/gcals)+(1-CRH)) # CRH changes taubkn, but CORT removes this change taubkn1=taubkns*(CRH*(taubknb/taubkns)+(1-CRH)) taubkn=taubkn1*(1-CORT) + taubkns*CORT gns1= gnss*(AVP*(gnsavp/gnss)+(1-AVP)) gns=gns1*(1-CORT) + gnscort*CORT # CRH changes kcabkn, but CORT removes this change kcabkn1=kcabkns*(CRH*(kcabknb/kcabkns)+(1-CRH)) kcabkn=kcabkn1*(1-CORT) + kcabkns*CORT # use auto=1 to make bifurcation diagram with Ca as parameter (cpar) par auto=0,cpar=0.8 vbkfar=vbk0-kshift*log(c/kcabkf) vbknear=vbk0-kshift*log(CaDOM/kcabkn) CaDOM= -A*(ica) aux CaDOM=CaDOM phik=1/(1+exp((vn-v)/sn)) phical=1/(1+exp((vm-v)/sm)) kirinf = 1/(1+exp((vir-v)/sr)) bkfarinf=1/(1+exp((vbkfar-v)/kbk)) bknearinf= 1/(1+exp((vbknear-v)/kbk)) # Ionic currents ica=gcal*phical*(v-vca) ikdr=gkdr*n*(v-vk) ins = gns*(v-vns) ikir = gir*kirinf*(v-vk) ibkfar = (1-KO)*gbkfar*bf*(v-vk) ibknear = (1-KO)*gbknear*bn*(v-vk) ik = ikdr + ibkfar + ibknear # noise wiener w inoise = sigmaN*w # domain calcium concentration cd=(1-auto)*c+auto*cpar v'= -(ica+ik+ins+ikir+inoise)/Cm n'= (phik-n)/taun c'= -ff*(alpha*ica+kc*c) bf'= (bkfarinf-bf)/taubkf bn'= (bknearinf-bn)/taubkn aux tsec=t/1000 @ dt=0.01, total=6000, maxstor=20000000, method=euler @ bounds=1000000000, xp=tsec, yp=v @ xlo=0, xhi=6, ylo=-75, yhi=20, bell=0 @ Ntst=70, Nmax=1000, Npr=1500, parmin=-1, parmax=200,Dsmax=0.2 done