adjust camkii on rate

ntumitolab · Nov 15, 2024 · bc80bfa · bc80bfa
1 parent 369a83d
commit bc80bfa
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Showing 6 changed files with 15 additions and 17 deletions.
diff --git 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
@@ -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
@@ -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
@@ -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
@@ -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
@@ -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