Tweaks to o'hara based models

c/bartolucci-2020.mmt

@@ -1,6 +1,6 @@
 [[model]]
 name: bartolucci-2020
-version: 20240815
+version: 20240816
 mmt_authors: Michael Clerx
 desc: """
     The 2020 "BPS" model of the human ventricular AP by Bartolucci et al. [1].
@@ -121,8 +121,8 @@ pace = 0 bind pace
 #
 [membrane]
 dot(V) = -(i_ion + stimulus.i_stim)
-    label membrane_potential
     in [mV]
+    label membrane_potential
 i_ion = (+ ina.INa
          + inal.INaL
          + ito.Ito
@@ -230,7 +230,7 @@ ENa = phys.RTF * log(extra.Na_o / sodium.Na_i)
     desc: Reversal potential for Sodium currents
 EK = phys.RTF * log(extra.K_o / potassium.K_i)
     in [mV]
-    desc: Reversal potential for Potassium currents
+    desc: Reversal potential for potassium currents
 PKNa = 0.01833
     desc: Permeability ratio K+ to Na+
 EKs = phys.RTF * log((extra.K_o + PKNa * extra.Na_o) / (potassium.K_i + PKNa * sodium.Na_i))
@@ -393,7 +393,7 @@ gto = 0.02 [mS/uF]
 fto = if(cell.mode == 0, 1, 4)
 # Everything except the V - EK below is shifted by 8mV
 Ito = fto * gto * (membrane.V - rev.EK) * ((1 - camk.f) * a * i + camk.f * ap * ip)
-    desc: Transient outward Potassium current
+    desc: Transient outward potassium current
     in [A/F]
 
 #
@@ -467,14 +467,14 @@ dot(CCa) = beta * OCa + psi * I2Ca - (omega + alpha) * CCa + r_up * C - r_down *
 OCa = 1 - CCa - I1Ca - I2Ca - C - I1 - I2 - O
 # Permeability
 fCa = piecewise(cell.mode == 0, 1, cell.mode == 1, 1.4, 2)
-PCa_base = 0.0001 [L/ms/F]
-    in [L/ms/F]
+PCa_base = 0.0001 [L/F/ms]
+    in [L/F/ms]
 PCa = 0.9 * fCa * PCa_base
-    in [L/ms/F]
+    in [L/F/ms]
 PNa = 0.00125 * PCa
-    in [L/ms/F]
+    in [L/F/ms]
 PK = 0.0003574 * PCa
-    in [L/ms/F]
+    in [L/F/ms]
 PhiCa = 4 * V * FFRT * (1.2 * Ca_ss * exp(2 * V * FRT) - 0.341 * Ca_o) / (exp(2 * V * FRT) - 1)
     in [mC/L]
 PhiNa =  V * FFRT * (0.75 * Na_ss * exp(V * FRT) - 0.75 * Na_o) / (exp(V * FRT) - 1)
@@ -637,12 +637,12 @@ gKs = 0.0034 [mS/uF]
     in [mS/uF]
 # Everything except V - E is shifted by EKshift
 IKs = fKs * gKs * KsCa * x1 * x2 * (membrane.V - rev.EKs)
-    desc: Slow delayed rectifier Potassium current
+    desc: Slow delayed rectifier potassium current
     in [A/F]
 
 #
 # IK1: Inward rectifier potassium current
-# Modified r gate, rescaled, and with the EKshift applied.
+# Modified rectification, rescaled, and with the EKshift applied.
 #
 [ik1]
 use extra.K_o
@@ -662,14 +662,13 @@ gK1 = 0.1908 [mS/uF]
 # Potential is shifted everywhere except in V - E
 IK1 = fK1 * gK1 * sqrt(K_o / 1 [mM]) * r * x * (membrane.V - rev.EK)
     in [A/F]
-    desc: Inward rectifier Potassium current
+    desc: Inward rectifier potassium current
 
 #
 # INaCa: Sodium/calcium exchange current
 # Rescaled but otherwise unchanged from [3]
 #
 [inaca]
-use membrane.V
 use extra.Na_o, extra.Ca_o
 use sodium.Na_i, calcium.Ca_i
 kna1 = 15 [mM]
@@ -691,9 +690,9 @@ kcaoff = 5e3 [1/s]
     in [1/s]
 qna = 0.5224
 qca = 0.167
-hca = exp(qca * V * phys.FRT)
-hna = exp(qna * V * phys.FRT)
-# Parameters h
+hca = exp(qca * membrane.V * phys.FRT)
+hna = exp(qna * membrane.V * phys.FRT)
+# h parameters
 h1 = 1 + Na_i / kna3 * (1 + hna)
 h2 = Na_i * hna / (kna3 * h1)
 h3 = 1 / h1
@@ -706,7 +705,7 @@ h9 = 1 / h7
 h10 = kasymm + 1 + Na_o / kna1 * (1 + Na_o / kna2)
 h11 = Na_o * Na_o / (h10 * kna1 * kna2)
 h12 = 1 / h10
-# Parameters k
+# k parameters
 k1 = h12 * Ca_o * kcaon
     in [1/s]
 k2 = kcaoff
@@ -762,7 +761,6 @@ INaCa = 0.8 * fNaCa * gNaCa * allo * (JncxNa + 2 * JncxCa)
 # Rescaled (via fNaCa) but otherwise unchanged from [3]
 #
 [inacass]
-use membrane.V
 use extra.Na_o, extra.Ca_o
 use sodium.Na_ss, calcium.Ca_ss
 use inaca.kna1, inaca.kna2, inaca.kna3, inaca.hna
@@ -831,8 +829,30 @@ INaCa_ss = 0.2 * inaca.fNaCa * inaca.gNaCa * allo * (JncxNa + 2 * JncxCa)
 #
 [inak]
 use membrane.V
-use extra.Na_o, sodium.Na_i, sodium.Na_ss
-use extra.K_o, potassium.K_i, potassium.K_ss
+use extra.Na_o, sodium.Na_i
+use extra.K_o, potassium.K_i
+MgATP = 9.8 [mM]
+    in [mM]
+    desc: Intracellular MgATP concentration
+MgADP = 0.05 [mM]
+    in [mM]
+    desc: Intracellular MgADP concentration
+eP = 4.2 [mM]
+    in [mM]
+    desc: The total concentration of inorganic phosphate (free + bound)
+H = 1e-4 [mM]
+    in [mM]
+    desc: Intracellular H+
+    note: Corrected to 1e-7 [M] (pH 7) from original value of 1e-7 [mM]
+Khp = 1.698e-7 [mM]
+    in [mM]
+    desc: Dissociation constant relating [HPi] and [H]
+Kxkur = 292 [mM]
+    in [mM]
+    desc: Dissociation constant relating [KPi] and [K]i
+Knap = 224 [mM]
+    in [mM]
+    desc: Dissociation constant relating [NaPi] and [Na]i
 k1p = 949.5 [1/s]
     in [1/s]
 k1m = 182.4 [1/s/mM]
@@ -849,54 +869,50 @@ k4p = 639 [1/s]
     in [1/s]
 k4m = 40 [1/s]
     in [1/s]
-Knai0 = 9.073 [mM]
-    in [mM]
 Knao0 = 27.78 [mM]
     in [mM]
-Kki = 0.5 [mM]
+    desc: Extracellular Na+ dissociation constant at 0mV
+Knai0 = 9.073 [mM]
     in [mM]
+    desc: Intracellular Na+ dissociation constant at 0mV
 Kko = 0.3582 [mM]
     in [mM]
-delta = -0.155
-MgADP = 0.05 [mM]
-    in [mM]
-MgATP = 9.8 [mM]
+    desc: Extracellular K+ dissociation constant
+Kki = 0.5 [mM]
     in [mM]
+    desc: Intracellular K+ dissociation constant
 Kmgatp = 1.698e-7 [mM]
     in [mM]
-H = 1e-4 [mM]
-    in [mM]
-    note: Corrected to 1e-7 [M] (pH 7) from original value of 1e-7 [mM]
-eP = 4.2 [mM]
-    in [mM]
-Khp = 1.698e-7 [mM]
-    in [mM]
-Knap = 224 [mM]
-    in [mM]
-Kxkur = 292 [mM]
-    in [mM]
-P = eP / (1 + H / Khp + Na_i / Knap + K_i / Kxkur)
-    in [mM]
+    desc: Intracellular MgATP dissociation constant
+delta = -0.155
+    desc: """A constant that "determines how the voltage dependence is
+             partitioned between intra and extracellular Na+ dissociation
+             reactions."""
+# Voltage-dependent Na+ dissociation constants
 Knai = Knai0 * exp(delta * V * phys.FRT / 3)
     in [mM]
 Knao = Knao0 * exp((1 - delta) * V * phys.FRT / 3)
     in [mM]
+# Forward (clockwise) rates
 a1 = k1p * (Na_i / Knai)^3 / ((1 + Na_i / Knai)^3 + (1 + K_i / Kki)^2 - 1)
     in [1/s]
-b1 = k1m * MgADP
-    in [1/s]
 a2 = k2p
     in [1/s]
-b2 = k2m * (Na_o / Knao)^3 / ((1 + Na_o / Knao)^3 + (1 + K_o / Kko)^2 - 1)
-    in [1/s]
 a3 = k3p * (K_o / Kko)^2 / ((1 + Na_o / Knao)^3 + (1 + K_o / Kko)^2 - 1)
     in [1/s]
-b3 = k3m * P * H / (1 + MgATP / Kmgatp)
-    in [1/s]
 a4 = k4p * MgATP / Kmgatp / (1 + MgATP / Kmgatp)
     in [1/s]
+# Backward (anticlockwise) rates
+b1 = k1m * MgADP
+    in [1/s]
+b2 = k2m * (Na_o / Knao)^3 / ((1 + Na_o / Knao)^3 + (1 + K_o / Kko)^2 - 1)
+    in [1/s]
+b3 = k3m * P * H / (1 + MgATP / Kmgatp)
+    in [1/s]
 b4 = k4m * (K_i / Kki)^2 / ((1 + Na_i / Knai)^3 + (1 + K_i / Kki)^2 - 1)
     in [1/s]
+P = eP / (1 + H / Khp + Na_i / Knap + K_i / Kxkur)
+    in [mM]
 x1 = a4 * a1 * a2 + b1 * b4 * b3 + a2 * b4 * b3 + b3 * a1 * a2
     in [s^-3]
     note: Corrected from the original code (b1 in second term)
@@ -906,8 +922,11 @@ x3 = a2 * a3 * a4 + b3 * b2 * b1 + b2 * b1 * a4 + a3 * a4 * b1
     in [s^-3]
 x4 = b4 * b3 * b2 + a3 * a4 * a1 + b2 * a4 * a1 + b3 * b2 * a1
     in [s^-3]
+# Cycle rate (obtained by writing any one of the four flux equations: they all
+# give the same result so that the pump count is conserved).
 r = (a1 * a2 * a3 * a4 - b1 * b2 * b3 * b4) / (x1 + x2 + x3 + x4)
     in [1/s]
+# Current
 JnakNa = 3 * r
     in [1/s]
 JnakK = -2 * r
@@ -917,7 +936,7 @@ PNaK = 30 [C/F]
     in [C/F]
 INaK = fNaK * PNaK * (JnakNa + JnakK)
     in [A/F]
-    desc: Sodium/Potassium ATPase current
+    desc: Sodium/potassium ATPase current
 
 #
 # IKb: Background potassium current
@@ -931,29 +950,29 @@ gKb = 0.003 [mS/uF]
     in [mS/uF]
 IKb = fKb * gKb * xkb * (V - rev.EK)
     in [A/F]
-    desc: Background Potassium current
+    desc: Background potassium current
 
 #
 # INab: Background sodium current
 # Unchanged from [3]
 #
 [inab]
 use membrane.V
-PNab = 3.75e-10 [L/ms/F]
-    in [L/ms/F]
+PNab = 3.75e-10 [L/F/ms]
+    in [L/F/ms]
 INab = PNab * V * phys.FFRT * (sodium.Na_i * evf - extra.Na_o) / (evf - 1)
     in [A/F]
     evf = exp(V * phys.FRT)
-    desc: Background Sodium current
+    desc: Background sodium current
 
 #
 # ICab: Background calcium current
 # Rescaled and GHK equation modified from [3]
 #
 [icab]
 use membrane.V
-PCab = 2.5e-8 [L/ms/F]
-    in [L/ms/F]
+PCab = 2.5e-8 [L/F/ms]
+    in [L/F/ms]
 ICab = PCab * 16 * V * phys.FFRT * (1.2 * calcium.Ca_i * evf2 - 0.341 * extra.Ca_o) / (evf2 - 1)
     in [A/F]
     evf2 = exp(2 * V * phys.FRT)
@@ -964,10 +983,10 @@ ICab = PCab * 16 * V * phys.FFRT * (1.2 * calcium.Ca_i * evf2 - 0.341 * extra.Ca
 # Unchanged from [3]
 #
 [ipca]
-GpCa = 0.0005 [A/F]
+gpCa = 0.0005 [A/F]
     in [A/F]
-IpCa = GpCa * calcium.Ca_i / (0.0005 [mM] + calcium.Ca_i)
-    desc: Sarcolemmal Calcium pump current
+IpCa = gpCa * calcium.Ca_i / (0.0005 [mM] + calcium.Ca_i)
+    desc: Sarcolemmal calcium pump current
     in [A/F]
 
 #
@@ -1053,7 +1072,7 @@ use cell.AFC, cell.vss, cell.vmyo
 INa_tot = ina.INa + inal.INaL + inab.INab + 3 * inaca.INaCa + 3 * inak.INaK
     in [A/F]
 dot(Na_i) = -INa_tot * AFC / vmyo + diff.JdiffNa * vss / vmyo
-    desc: Intracellular Potassium concentration
+    desc: Intracellular potassium concentration
     in [mM]
 INa_ss_tot = ical.ICaNa + 3 * inacass.INaCa_ss
     in [A/F]
@@ -1078,7 +1097,7 @@ IK_tot = (
 IK_ss_tot = ical.ICaK
     in [A/F]
 dot(K_i) = -(IK_tot + stimulus.i_stim) * AFC / vmyo + diff.JdiffK * vss / vmyo
-    desc: Intracellular Potassium concentration
+    desc: Intracellular potassium concentration
     in [mM]
 dot(K_ss) = -IK_ss_tot * AFC / vss - diff.JdiffK
     desc: Potassium concentration in the T-Tubule subspace