diff --git a/docs/bcl.jl b/docs/bcl.jl index 688c3b7..ebc6cf6 100644 --- a/docs/bcl.jl +++ b/docs/bcl.jl @@ -50,7 +50,7 @@ plot(sol2, idxs=[sys.Cai_sub_SR, sys.Cai_sub_SL, sys.Cai_mean], tspan=(299, 300) plot(sol2, idxs=sys.CaMKAct, title="Active CaMKII") # ## Comparing 1-2 Hz -plot(sol, idxs=sys.vm*1000, title="Action potential", lab="1Hzf") +plot(sol, idxs=sys.vm*1000, title="Action potential", lab="1Hz") plot!(sol2, idxs=sys.vm*1000, lab="2Hz", tspan=(299, 300), xlabel="Time (sec.)", ylabel="Voltage (mV)") #--- diff --git a/docs/camk-sens.jl b/docs/camk-sens.jl index 5dbb58f..c334126 100644 --- a/docs/camk-sens.jl +++ b/docs/camk-sens.jl @@ -18,8 +18,7 @@ equations(sys) #--- prob = SteadyStateProblem(sys, [sys.k_phosCaM => 0]) alg = DynamicSS(Rodas5P()) -logrange(0.01μM, 10μM, length=101) -ca = logrange(0.03μM, 10μM, length=101) +ca = logrange(0.1μM, 10μM, length=101) prob_func = (prob, i, repeat) -> begin remake(prob, p=[Ca => ca[i]]) end diff --git a/docs/camk-simp.jl b/docs/camk-simp.jl index 3db5e9b..fc0f8ce 100644 --- a/docs/camk-simp.jl +++ b/docs/camk-simp.jl @@ -7,7 +7,7 @@ using DiffEqCallbacks using Plots using LsqFit using CaMKIIModel -using CaMKIIModel: μM, hil +using CaMKIIModel: μM, hil, Hz Plots.default(lw=1.5) #--- @@ -24,8 +24,8 @@ stimend = 300.0 alg = FBDF() @unpack Istim = sys callback = build_stim_callbacks(Istim, stimend; period=1, starttime=stimstart) -prob = ODEProblem(sys, [], tend) -prob_simp = ODEProblem(sys_simp, [], tend) +prob = ODEProblem(sys, [sys.kCaM4_on => 15Hz / μM, sys.kCaM2C_on => 0.5Hz / μM], tend) +prob_simp = ODEProblem(sys_simp, [sys_simp.kCaM4_on => 15Hz / μM, sys_simp.kCaM2C_on => 0.5Hz / μM], tend) #--- @time sol = solve(prob, alg; callback, abstol=1e-6, reltol=1e-6) @@ -39,7 +39,6 @@ plot!(sol_simp, idxs=sys.vm*1000, tspan=(295, 300), label= "Simplified model", l plot(sol, idxs=sys.CaMKAct, label= "Full model", title="Active CaMKII") plot!(sol_simp, idxs=sys_simp.CaMKAct, label= "Simplified model", line=:dash) - # PCaM too high @unpack CaM, KCaM, PCaM, CaMK = sys_simp @unpack CaM0, CaM2C, CaM2N, CaM4, CaM0_CaMK, CaM2C_CaMK, CaM2N_CaMK, CaM4_CaMK, CaM0_CaMKP, CaM2C_CaMKP, CaM2N_CaMKP, CaM4_CaMKP = sys_simp diff --git a/src/camkii_ros.jl b/src/camkii_ros.jl index 85245a1..73d4cbc 100644 --- a/src/camkii_ros.jl +++ b/src/camkii_ros.jl @@ -39,11 +39,11 @@ function get_camkii_sys(Ca=0μM; ## CaM binding to CaMKII kCaM0_on = 3.8Hz / mM kCaM0_off = 5.5Hz - kCaM2C_on = 0.92Hz / μM + kCaM2C_on = 0.5Hz / μM # 0.92 μM-1s-1 kCaM2C_off = 6.8Hz kCaM2N_on = 0.12Hz / μM kCaM2N_off = 1.7Hz - kCaM4_on = 30Hz / μM # 14-60 uM-1s-1 + kCaM4_on = 15Hz / μM # 14-60 uM-1s-1 kCaM4_off = 1.5Hz # 1.1 - 2.3 s-1 kCaM0P_on = kCaM0_on * binding_To_PCaMK kCaM2CP_on = kCaM2C_on * binding_To_PCaMK @@ -208,10 +208,10 @@ function get_camkii_fast_ca_binding_sys(Ca=0μM; kCaM2C_off = 6.8Hz kCaM2N_off = 1.7Hz kCaM4_off = 1.5Hz - kCaM0P_on = kCaM0_on - kCaM2CP_on = kCaM2C_on - kCaM2NP_on = kCaM2N_on - kCaM4P_on = kCaM4_on + kCaM0P_on = kCaM0_on * binding_To_PCaMK + kCaM2CP_on = kCaM2C_on * binding_To_PCaMK + kCaM2NP_on = kCaM2N_on * binding_To_PCaMK + kCaM4P_on = kCaM4_on * binding_To_PCaMK kCaM0P_off = inv(3second) kCaM2CP_off = inv(3second) kCaM2NP_off = inv(3second) @@ -300,7 +300,7 @@ function get_camkii_fast_ca_binding_sys(Ca=0μM; add_raw_rate!(rates, vf1 - vr1, [CaMK, CaM], [KCaM]) ## CaM + CaMKP <--> PCaM - vf2 = binding_To_PCaMK * CaMKP * (kCaM0P_on * CaM0 + kCaM2CP_on * CaM2C + kCaM2NP_on * CaM2N + kCaM4P_on * CaM4) + vf2 = CaMKP * (kCaM0P_on * CaM0 + kCaM2CP_on * CaM2C + kCaM2NP_on * CaM2N + kCaM4P_on * CaM4) vr2 = kCaM0P_off * CaM0_CaMKP + kCaM2CP_off * CaM2C_CaMKP + kCaM2NP_off * CaM2N_CaMKP + kCaM4P_off * CaM4_CaMKP add_raw_rate!(rates, vf2 - vr2, [CaMKP, CaM], [PCaM]) @@ -310,7 +310,7 @@ function get_camkii_fast_ca_binding_sys(Ca=0μM; add_raw_rate!(rates, vf3 - vr3, [CaMKOX, CaM], [OCaM]) ## CaM + CaMKPOX <--> OPCaM - vf4 = binding_To_PCaMK * CaMKPOX * (kCaM0P_on * CaM0 + kCaM2CP_on * CaM2C + kCaM2NP_on * CaM2N + kCaM4P_on * CaM4) + vf4 = CaMKPOX * (kCaM0P_on * CaM0 + kCaM2CP_on * CaM2C + kCaM2NP_on * CaM2N + kCaM4P_on * CaM4) vr4 = kCaM0P_off * CaM0_CaMKPOX + kCaM2CP_off * CaM2C_CaMKPOX + kCaM2NP_off * CaM2N_CaMKPOX + kCaM4P_off * CaM4_CaMKPOX add_raw_rate!(rates, vf4 - vr4, [CaMKPOX, CaM], [OPCaM]) diff --git a/src/capde.jl b/src/capde.jl index cace977..f0ed5e4 100644 --- a/src/capde.jl +++ b/src/capde.jl @@ -17,7 +17,7 @@ function get_ca_pde_sys(; @parameters begin Dca = 7μm^2 / ms TrpnTotal = 35μM # Half of adult rat CMC (70 μM) - CmdnTotal = 50μM + CmdnTotal = 30μM KmCmdn = 2.38μM KmTrpn = 0.5μM fracTnIp0 = 0.062698 # Baseline effect diff --git a/src/ica.jl b/src/ica.jl index f11d4fe..a9baf9c 100644 --- a/src/ica.jl +++ b/src/ica.jl @@ -8,7 +8,7 @@ function get_ica_sys(nai, cai, nao, cao, vm; LCCb_PKAp=0, name=:icasys) kNaCa = 2.268e-16μAμF / μM^4 dNaCa = 1e-16 / μM^4 gNaCa = 0.5 - GCaL = 1.3e-4 * (metre^3 / second / Farad) # 6.3e-5 + GCaL = 1e-4 * (metre^3 / second / Farad) # 6.3e-5 taufca = 10ms gCaT = 0.2mSμF gCab = 0.0008mSμF