The PKA-pathway-related proteins and signalling molecules are highlighted by blue, PKC-pathway molecules by yellow, and CaMKII-pathway molecules by green colours. Reactions associated with a …
(A) Illustration of the stimulus protocols with Ca2+ flux amplitudes 150 (green), 200 (cyan), and 250 (purple) particles/ms. (B–F) Time courses of Ca2+ (in nM) bound to buffers (B), pumps (C), …
(A) Total synaptic conductance in response to 4xHFS, determined by the numbers of membrane-inserted GluR1s and GluR2s — see Equation 5. The stimulation starts at 40 s and lasts until 53 s. (B–C) …
(A) When GluR1 subunits are absent, 4xHFS induces LTD instead of LTP. (B) When GluR2 subunits are absent, LFS does not lead to changes in synaptic conductance. (C) When GluR1 subunits are absent, …
(A) Plasticity induced by HFS and LFS. The y-axis shows the total synaptic conductance, and the x-axis shows the time. The 4xHFS stimulation lasts from 40 to 53 s, and the LFS stimulation from 40 to …
The 6xHFSt protocol lasts from 0 to 60 s, while the LFS-1Hz protocol lasts from 0 to 1800s (data shown until 500 s). See Materials and methods, section 'Modelling the Ca2+ inputs and neuromodulatory …
In the control case, the pre-synaptic input-associated fluxes of β-adrenergic and cholinergic ligands were 10 and 20 particles/ms, respectively, and the duration of each pulse was 3 ms. Here, the …
(A–D) 4xHFS-induced LTP in the control case (dark purple), without Ca2+ inputs (blue), without β-adrenergic ligands (green), and under blockade of PKC pathway-activation (mGluRs or cholinergic …
(A) Layer 2/3 pyramidal cell morphology (grey, thin), locations of synaptic input highlighted (black, thick). Inset: Illustration of the inputs (black) and the recorded synaptic intracellular Ca2+ …
(A–D) The Ca2+ flux time course during the pairing protocol (from 100 ms before to 900 ms after the pre-synaptic stimulus) entering the post-synaptic spine through NMDA receptors when the onset of …
The y-axis shows the post-STDP synaptic conductance (in presence of β-adrenergic and cholinergic neuromodulation) relative to baseline as in Figure 5M. (A) The x-axis shows the peak Ca2+ input (in …
(A) The LTP/LTD curves for all 16 classes. Four values of Ca2+ input amplitude were considered: 0, 50, 150, and 250 particles/ms (x-axis; repeated and overlaid for space). The y-axis shows the …
Values of initial concentrations (47 parameters) or reaction rates (223 parameters) were changed one at the time by −10% or +10%, and the resulting synaptic conductance 16 min after LFS (A) or 4xHFS …
(A) The model could be fit to LTP/LTD data from data sets EC-1 (top), EC-2, PFC-1, PFC-2, BC, ACC, PFC-3, AuC-1, and AuC-2 (bottom). The curves represent the model predictions of the best-fit …
Ranges of each parameter among the accepted parameter sets from the fitting of Figure 9. All parameters are linearly scaled between 0 and 1, which represent the minimal and maximal value of the …
See Figure 9—figure supplement 1 for details.
See Figure 9—figure supplement 1 for details.
See Figure 9—figure supplement 1 for details.
See Figure 9—figure supplement 1 for details.
See Figure 9—figure supplement 1 for details.
See Figure 9—figure supplement 1 for details.
See Figure 9—figure supplement 1 for details.
See Figure 9—figure supplement 1 for details.
See Figure 9—figure supplement 1 for details.
See Figure 9—figure supplement 1 for details.
(A) The predicted responses of the 20 best models in each data set to HFS (100 pulses at 100 Hz) stimulation. (B–D) The predicted responses of the 20 best models in each data set to the applied …
Black curves represent the final model, while grey lines represent predictions of models where previous model components or tentative parameter values were used. (A) Concentration of …
The model was run for 4040 s without inputs. The absolute values of the time derivatives for each molecular species were determined, and the black curve shows the sum of these derivatives (nM/sec) …
(A) Experimental evidence on the requirement of various molecular species for specific types of synaptic regulation in different cortical areas. (B) Model components needed for describing the modes …
(A) | ||||
---|---|---|---|---|
Pathway components | Type of neurons | Type of regulation | Pre-/post-synaptic | References |
CaMKII | Cingulate cortex | Esophageal acid-induced sensitisation | post-syn. | Banerjee et al., 2013 |
CaMKII | Prefrontal cortex, pyramidal neurons | 5-HT1-induced modulation of AMPA currents | post-syn. | Cai et al., 2002 |
-adr. receptors, PKA | Visual cortex, layer 4 pyramidal cells | Potentiation of AMPA currents | post-syn. | Seol et al., 2007 |
M1 receptors, PKC | Visual cortex, layer 4 pyramidal cells | Depression of AMPA currents | post-syn. | Seol et al., 2007 |
D1–PKA | Prefrontal cortex, pyramidal neurons | Potentiation of AMPA currents | post-syn. | Sun et al., 2005 |
-adr. receptors | Frontal cortex | Potentiation of field EPSPs | n/a | Sáez-Briones et al., 2015 |
PKC | Cultured cortical neurons | Internalisation of AMPARs | post-syn. | Chung et al., 2000 |
ERK | Visual cortex | Potentiation of field EPSPs | n/a | Di Cristo et al., 2001 |
(B) | ||||
Molecular pathway | Cell type and references | |||
Ca2+ → CaM → CaMKII | Hippocampal CA1 neuron Bhalla and Iyengar, 1999; Jȩdrzejewska-Szmek et al., 2017, generic Hayer and Bhalla, 2005, | |||
cerebellar Purkinje cells Gallimore et al., 2018, striatal spiny projection neuron Blackwell et al., 2019 | ||||
CaMKII → GluR1 S831p | Hippocampal CA1 neuron Jȩdrzejewska-Szmek et al., 2017 | |||
-adrenergic receptors → cAMP | Hippocampal CA1 neuron Jȩdrzejewska-Szmek et al., 2017 | |||
cAMP → PKA | Hippocampal CA1 neuron Bhalla and Iyengar, 1999; Jȩdrzejewska-Szmek et al., 2017, cerebellar Purkinje | |||
cells Gallimore et al., 2018 | ||||
PKA → GluR1 S845p | Hippocampal CA1 neuron Jȩdrzejewska-Szmek et al., 2017 | |||
M1 receptors → PLC | Cerebellar Purkinje cells Gallimore et al., 2018 | |||
PLC → PKC | Hippocampal CA1 neuron Bhalla and Iyengar, 1999, striatal spiny projection neuron | |||
Kim et al., 2013; Blackwell et al., 2019 | ||||
cerebellar Purkinje cells Kotaleski et al., 2002; Gallimore et al., 2018 | ||||
PKC → GluR2 S880p | Cerebellar Purkinje cells Gallimore et al., 2018 |
The first column labels the experimental data set and names the underlying study. The second column shows the considered synaptic pathway and the third column shows whether the observed LTP/LTD had …
Data set | Reference | Pathway | Pre/post | Freq. | Npulses | Experiment | 10 min | 15 min | 20 min | SD |
---|---|---|---|---|---|---|---|---|---|---|
EC-1 | Ma et al., 2008 | horizontal | mostly | 100 | 100 | control | 1.3 | 1.4 | 1.3 | 0.1 |
post | CaMKII blocked | 1.05 | 1.02 | 0.95 | 0.07 | |||||
without post-syn. Ca2+ | 1.05 | 1.05 | 1.1 | 0.09 | ||||||
EC-2 | Ma et al., 2008 | ascending | mostly | 100 | 100 | control | 1.6 | 1.6 | 1.6 | 0.11 |
post | PKA blocked | 1.4 | 1.4 | 1.4 | 0.13 | |||||
without post-syn. Ca2+ | 1.3 | 1.4 | 1.4 | 0.13 | ||||||
PFC-1 | Sáez-Briones et al., 2015 | CC→PFC | n/a | 312 | 156 | control | 2.0 | 1.98 | 1.9 | 0.08 |
without -adrenergic ligand | 1.34 | 1.4 | 1.36 | 0.09 | ||||||
PFC-2 | Flores et al., 2011 | CC→PFC | n/a | 312 | 156 | control | 1.7 | 1.6 | 1.64 | 0.12 |
without −1-receptor agonist | 1.43 | 1.45 | 1.43 | 0.1 | ||||||
BC | Hardingham et al., 2003 | L4→L2/3 | n/a | 5 | 10 × 4 | control | 1.35 | 1.4 | 1.3 | 0.09 |
CaMKII mutant | 1.25 | 1.2 | 1.1 | 0.09 | ||||||
ACC | Song et al., 2017 | L5/6 → L2/3 | post | 5 | 10 × 4 | control | 1.55 | 1.4 | 1.4 | 0.05 |
without s845 | 1.1 | 1.05 | 1.05 | 0.07 | ||||||
without s831 | 1.35 | 1.4 | 1.3 | 0.1 | ||||||
PFC-3 | Zhou et al., 2013 | L2/3 → L2/3 | mostly | 0.1 | 50 | control | 1.3 | 1.4 | 1.4 | 0.14 |
post | without −1-receptor agonist | 1.1 | 1.2 | 1.2 | 0.13 | |||||
VC-1 | Kirkwood et al., 1997 | L4 → L3 | n/a | 5 | 10 × 4 | (CTR, HFS) | 1.3 | 1.26 | 1.26 | 0.07 |
(adult) | (without CaMKII, HFS) | 1.02 | 1.02 | 1.02 | 0.02 | |||||
5 | 900* | (CTR, LFS) | n/a | 0.95 | 0.95 | 0.05 | ||||
(without CaMKII, LFS) | n/a | 0.88 | 0.93 | 0.03 | ||||||
VC-2 | Kirkwood et al., 1997 | L4 → L3 | n/a | 5 | 10 × 4 | (CTR, HFS) | 1.2 | 1.18 | 1.18 | 0.05 |
(4–5 w) | (without CaMKII, HFS) | 1.07 | 1.09 | 1.08 | 0.03 | |||||
5 | 900* | (CTR, LFS) | n/a | 0.79 | 0.82 | 0.03 | ||||
(without CaMKII, LFS) | n/a | 0.82 | 0.89 | 0.03 | ||||||
AuC-1 | Kotak et al., 2007 | L6 → L5 | n/a | 1 | 25 × 5 | LTP-expressing cells | 1.98 | 1.58 | 1.93 | 0.19 |
AuC-2 | Kotak et al., 2007 | L6 → L5 | n/a | 1 | 25 × 5 | LTD-expressing cells | 0.77 | 0.68 | 0.67 | 0.09 |
(A) The reaction-rate units are in 1/ms, 1/(nMms), 1/(nM2ms), 1/(nM3ms), or 1/(nM4ms), depending on the number of reactants. Reactions are grouped by similar modes of action and identical forward …
(A) | Forw. | Backw. | Forw. | Backw. | |||
---|---|---|---|---|---|---|---|
ID | Reaction | Rate | Rate | ID | Reaction | Rate | Rate |
1 | Ca + PMCA ⇌ PMCACa | 5e-05 | 0.007 | 71 | GluR1 + ⇌ GluR1 | 2.78e-08 | 0.002 |
2 | PMCACa ⇌ PMCA + CaOut | 0.0035 | 0.0 | 72 | GluR1 ⇌ GluR1 + | 0.0005 | 0 |
3 | Ca + NCX ⇌ NCXCa | 1.68e-05 | 0.0112 | 73 | GluR1 + PKAc ⇌ GluR1 | 4e-06 | 0.024 |
4 | NCXCa ⇌ NCX + CaOut | 0.0056 | 0.0 | 74 | GluR1 + PP1 ⇌ GluR1 | 8.7e-07 | 0.00068 |
5 | CaOut + Leak ⇌ CaOutLeak | 1.5e-06 | 0.0011 | 75 | GluR1 ⇌ GluR1 + PP1 | 0.00017 | 0 |
6 | CaOutLeak ⇌ Ca + Leak | 0.0011 | 0.0 | 76 | GluR1 + PP1 ⇌ GluR1 | 8.75e-07 | 0.0014 |
7 | Ca + Calbin ⇌ CalbinC | 2.8e-05 | 0.0196 | 77 | GluR1 ⇌ GluR1 + PP1 | 0.00035 | 0 |
8 | L ⇌ LOut | 0.0005 | 2e-09 | 78 | GluR1 + PP2BCaMCa4 ⇌ GluR1 | 2.01e-06 | 0.008 |
9 | L + R ⇌ LR | 5.555e-06 | 0.005 | 79 | GluR1 ⇌ GluR1 + PP2BCaMCa4 | 0.002 | 0 |
10 | LR + Gs ⇌ LRGs | 6e-07 | 1e-06 | 80 | GluR1 ⇌ GluR1_memb | 2e-07 | 8e-07 |
11 | Gs + R ⇌ GsR | 4e-08 | 3e-07 | 81 | GluR1_S845 | ||
12 | GsR + L ⇌ LRGs | 2.5e-06 | 0.0005 | ⇌ GluR1_memb_S845 | 3.28e-05 | 8e-06 | |
13 | LRGs ⇌ LRGsbg + GsaGTP | 0.02 | 0.0 | 82 | PDE1 + CaMCa4 ⇌ PDE1CaMCa4 | 0.0001 | 0.001 |
14 | LRGsbg ⇌ LR + Gsbg | 0.08 | 0.0 | 83 | PDE1CaMCa4 + cAMP ⇌ PDE1CaMCa4cAMP | 4.6e-06 | 0.044 |
15 | + PKAc ⇌ PKAc | 8e-07 | 0.00448 | 84 | PDE1CaMCa4cAMP ⇌ PDE1CaMCa4 + AMP | 0.011 | 0.0 |
16 | PKAc ⇌ p + PKAc | 0.001 | 0.0 | 85 | AMP ⇌ ATP | 0.001 | 0.0 |
17 | ppLR + PKAc ⇌ PKAcppLR | 1.712e-05 | 0.00448 | 86 | PDE4 + cAMP ⇌ PDE4cAMP | 2.166e-05 | 0.0034656 |
18 | pppLR + PKAc ⇌ PKAcpppLR | 0.001712 | 0.00448 | 87 | PDE4cAMP ⇌ PDE4 + AMP | 0.017233 | 0.0 |
19 | ppppLR + Gi ⇌ ppppLRGi | 0.00015 | 0.00025 | 88 | + ⇌ PKAc | 2.5e-07 | 8e-05 |
20 | ppppLRGi ⇌ ppppLRGibg + GiaGTP | 0.000125 | 0.0 | 89 | PKAc ⇌ pPDE4 + PKAc | 2e-05 | 0.0 |
21 | pppp ⇌ pppp + Gibg | 0.001 | 0.0 | 90 | pPDE4 ⇌ PDE4 | 2.5e-06 | 0.0 |
22 | p ⇌ | 2.5e-06 | 0.0 | 91 | pPDE4 + cAMP ⇌ pPDE4cAMP | 0.000433175 | 0.069308 |
23 | pp ⇌ p | 2.5e-06 | 0.0 | 92 | pPDE4cAMP ⇌ pPDE4 + AMP | 0.3446674 | 0.0 |
24 | R + PKAc ⇌ PKAcR | 4e-08 | 0.00448 | 93 | PKAcAMP4 ⇌ PKAr + 2*PKAc | 0.00024 | 2.55e-05 |
25 | pR + PKAc ⇌ PKAcpR | 4e-07 | 0.00448 | 94 | Ca + fixedbuffer ⇌ fixedbufferCa | 0.0004 | 20.0 |
26 | ppR + PKAc ⇌ PKAcppR | 4e-06 | 0.00448 | 95 | Glu ⇌ GluOut | 0.0005 | 2e-10 |
27 | pppR + PKAc ⇌ PKAcpppR | 0.0004 | 0.00448 | 96 | Ca + PLC ⇌ PLCCa | 4e-07 | 0.001 |
28 | ppppR + Gi ⇌ ppppRGi | 7.5e-05 | 0.000125 | 97 | GqaGTP + PLC ⇌ PLCGqaGTP | 7e-07 | 0.0007 |
29 | ppppRGi ⇌ ppppRGibg + GiaGTP | 6.25e-05 | 0.0 | 98 | Ca + PLCGqaGTP ⇌ PLCCaGqaGTP | 8e-05 | 0.04 |
30 | GsaGTP ⇌ GsaGDP | 0.01 | 0.0 | 99 | GqaGTP + PLCCa ⇌ PLCCaGqaGTP | 0.0001 | 0.01 |
31 | GsaGDP + Gsbg ⇌ Gs | 0.1 | 0.0 | 100 | PLCCa + Pip2 ⇌ PLCCaPip2 | 3e-08 | 0.01 |
32 | GiaGTP ⇌ GiaGDP | 0.000125 | 0.0 | 101 | PLCCaPip2 ⇌ PLCCaDAG + Ip3 | 0.0003 | 0.0 |
33 | GiaGDP + Gibg ⇌ Gi | 0.00125 | 0.0 | 102 | PLCCaDAG ⇌ PLCCa + DAG | 0.2 | 0.0 |
34 | GsaGTP + AC1 ⇌ AC1GsaGTP | 3.85e-05 | 0.01 | 103 | PLCCaGqaGTP + Pip2 ⇌ PLCCaGqaGTPPip2 | 1.5e-05 | 0.075 |
35 | AC1 + CaMCa4 ⇌ AC1 | 6e-06 | 0.0009 | 104 | PLCCaGqaGTPPip2 ⇌ PLCCaGqaGTPDAG + Ip3 | 0.25 | 0.0 |
36 | + ATP ⇌ | 1e-05 | 2.273 | 105 | PLCCaGqaGTPDAG ⇌ PLCCaGqaGTP + DAG | 1.0 | 0.0 |
37 | AC1GsaGTPCaMCa4ATP | 106 | Ip3degrad + PIkinase ⇌ Ip3degPIk | 2e-06 | 0.001 | ||
⇌ cAMP + AC1GsaGTPCaMCa4 | 0.02842 | 0.0 | 107 | Ip3degPIk ⇌ PIkinase + Pip2 | 0.001 | 0.0 | |
38 | + ⇌ AC1Gsa | 6.25e-05 | 0.01 | 108 | PLC ⇌ PLC + GqaGDP | 0.012 | 0.0 |
39 | ⇌ cAMP + | 0.002842 | 0.0 | 109 | GqaGTP ⇌ GqaGDP | 0.001 | 0.0 |
40 | AC1GiaGTPCaMCa4ATP | 110 | GqaGDP ⇌ Gqabg | 0.01 | 0.0 | ||
⇌ cAMP + AC1GiaGTPCaMCa4 | 0.0005684 | 0.0 | 111 | Ca + DGL ⇌ CaDGL | 0.000125 | 0.05 | |
41 | AC1CaMCa4ATP ⇌ cAMP + AC1CaMCa4 | 0.005684 | 0.0 | 112 | DAG + CaDGL ⇌ DAGCaDGL | 5e-07 | 0.001 |
42 | AC8 + CaMCa4 ⇌ AC8CaMCa4 | 1.25e-06 | 0.001 | 113 | DAGCaDGL ⇌ CaDGL + 2AG | 0.00025 | 0.0 |
43 | CaM + 2*Ca ⇌ CaMCa2 | 1.7e-08 | 0.035 | 114 | Ip3 ⇌ Ip3degrad | 0.01 | 0.0 |
44 | + Ca ⇌ | 1.4e-05 | 0.228 | 115 | 2AG ⇌ 2AGdegrad | 0.005 | 0.0 |
45 | + Ca ⇌ | 2.6e-05 | 0.064 | 116 | DAG + DAGK ⇌ DAGKdag | 7e-08 | 0.0008 |
46 | CaM + Ng ⇌ NgCaM | 2.8e-05 | 0.036 | 117 | DAGKdag ⇌ DAGK + PA | 0.0002 | 0.0 |
47 | CaM + PP2B ⇌ PP2BCaM | 4.6e-06 | 1.2e-06 | 118 | Ca + PKC ⇌ PKCCa | 1.33e-05 | 0.05 |
48 | CaMCa + PP2B ⇌ PP2B | 4.6e-05 | 1.2e-06 | 119 | PKCCa + DAG ⇌ PKCt | 1.5e-08 | 0.00015 |
49 | PP2BCaM + 2*Ca ⇌ PP2BCaMCa2 | 1.7e-07 | 0.35 | 120 | Glu + MGluR ⇌ MGluR_Glu | 1.68e-08 | 0.0001 |
50 | CaMCa4 + CK ⇌ CKCaMCa4 | 1e-05 | 0.003 | 121 | MGluR_Glu ⇌ MGluR_Glu_desens | 6.25e-05 | 1e-06 |
51 | 2*CKCaMCa4 ⇌ Complex | 1e-07 | 0.01 | 122 | Gqabg + MGluR_Glu ⇌ MGluR_Gqabg_Glu | 9e-06 | 0.00136 |
52 | CKpCaMCa4 + CKCaMCa4 ⇌ pComplex | 1e-07 | 0.01 | 123 | MGluR_Gqabg_Glu ⇌ GqaGTP + MGluR_Glu | 0.0015 | 0.0 |
53 | CK + Complex ⇌ CK + pComplex | 1e-07 | 0.0 | 124 | GluR2 + PKC ⇌ GluR2 | 4e-07 | 0.0008 |
54 | 2*Complex ⇌ Complex + pComplex | 1e-05 | 0.0 | 125 | GluR2 ⇌ GluR2 + PKC | 0.0047 | 0 |
55 | Complex + pComplex ⇌ 2*pComplex | 3e-05 | 0.0 | 126 | GluR2 + PP2A ⇌ GluR2 | 5e-07 | 0.005 |
56 | CKpCaMCa4 ⇌ CaMCa4 + CKp | 8e-07 | 1e-05 | 127 | GluR2 ⇌ GluR2 + PP2A | 0.00015 | 0 |
57 | CKp + PP1 ⇌ CKp | 4e-09 | 0.00034 | 128 | GluR2 ⇌ GluR2_memb | 0.00024545 | 0.0003 |
58 | CKp ⇌ PP1 + CK | 8.6e-05 | 0.0 | 129 | GluR2_S880 ⇌ GluR2_memb_S880 | 0.0055 | 0.07 |
59 | PKA + 4*cAMP ⇌ PKAcAMP4 | 1.6e-15 | 6e-05 | 130 | ACh + M1R ⇌ AChM1R | 9.5e-08 | 0.0025 |
60 | Epac1 + cAMP ⇌ Epac1cAMP | 3.1e-08 | 6.51e-05 | 131 | Gqabg + AChM1R ⇌ AChM1RGq | 2.4e-05 | 0.00042 |
61 | I1 + PKAc ⇌ I1PKAc | 1.4e-06 | 0.0056 | 132 | Gqabg + M1R ⇌ M1RGq | 5.76e-07 | 0.00042 |
62 | I1PKAc ⇌ Ip35 + PKAc | 0.0014 | 0.0 | 133 | ACh + M1RGq ⇌ AChM1RGq | 3.96e-06 | 0.0025 |
63 | Ip35 + PP1 ⇌ Ip35PP1 | 1e-06 | 1.1e-06 | 134 | AChM1RGq ⇌ GqaGTP + AChM1R | 0.0005 | 0.0 |
64 | Ip35 + PP2BCaMCa4 ⇌ Ip35PP2B | 9.625e-05 | 0.33 | 135 | ACh ⇌ | 0.006 | 0 |
65 | Ip35PP2B ⇌ I1 + PP2B | 0.055 | 0.0 | 136 | Ca + PLA2 ⇌ CaPLA2 | 6e-07 | 0.003 |
66 | PP1PP2BCaMCa4 ⇌ PP1 + PP2BCaMCa4 | 0.0015 | 0.0 | 137 | CaPLA2 + Pip2 ⇌ CaPLA2Pip2 | 2.2e-05 | 0.444 |
67 | GluR1 + PKAc ⇌ GluR1 | 4.02e-06 | 0.024 | 138 | CaPLA2Pip2 ⇌ CaPLA2 + AA | 0.111 | 0.0 |
68 | GluR1 ⇌ GluR1 + PKAc | 0.006 | 0 | 139 | AA ⇌ Pip2 | 0.001 | 0.0 |
69 | GluR1 + CK ⇌ GluR1 | 2.224e-08 | 0.0016 | 140 | PKCt + AA ⇌ PKCp | 5e-09 | 1.76e-07 |
70 | GluR1 ⇌ GluR1 + CK | 0.0004 | 0 |
(B) | |||||||
---|---|---|---|---|---|---|---|
∈ {LR, pLR} | (, , ) ∈ { (_CKpCam, _S831, CKpCaMCa4), (_PKCt, | ||||||
∈ {LR, pLR, ppLR, pppLR, R, pR, ppR, pppR} | _S831, PKCt), (_PKCp, _S831, PKCp), (_S845_CKpCam, _S845_S831, | ||||||
(, ) ∈ { (LRGibg, LR), (RGibg, R) } | CKpCaMCa4), (_S845_PKCt, _S845_S831, PKCt), (_S845_PKCp, | ||||||
∈ {LR, R, pR} | _S845_S831, PKCp), (_memb_CKpCam, _memb_S831, CKpCaMCa4), | ||||||
∈ {LR, pLR, ppLR, pR, ppR} | (_memb_PKCt, _memb_S831, PKCt), (_memb_PKCp, _memb_S831, PKCp), | ||||||
(, ) ∈ { (GsaGTP, GsaGTPCaMCa4), (GsaGTPGiaGTP, | (_memb_S845_CKpCam, _memb_S845_S831, CKpCaMCa4), | ||||||
GsaGTPGiaGTPCaMCa4), (, CaMCa4) } | (_memb_S845_PKCt, _memb_S845_S831, PKCt), (_memb_S845_PKCp, | ||||||
(, ) ∈ { (AC1GsaGTPCaMCa4, AC1GsaGTPCaMCa4ATP), | _memb_S845_S831, PKCp) } | ||||||
(AC1GsaGTPGiaGTPCaMCa4, AC1GsGiCaMCa4ATP), (AC1GiaGTPCaMCa4, | (, ) ∈ { (_S831, _S831_PKAc), (_memb_S831, | ||||||
AC1GiaGTPCaMCa4ATP), (AC1CaMCa4, AC1CaMCa4ATP), (AC8CaMCa4, | _memb_S831_PKAc) } | ||||||
AC8CaMCa4ATP) } | (, ) ∈ { (_S845, _S845_PP1), (_memb_S845, | ||||||
(, , ) ∈ { (GiaGTP, AC1GsaGTP, GTPGiaGTP), (GiaGTP, | _memb_S845_PP1) } | ||||||
AC1CaMCa4, GTPCaMCa4), (AC1GiaGTP, GsaGTP, GTPGiaGTP) } | (, ) ∈ { (_S845_PP1, ), (_memb_S845_PP1, | ||||||
(, ) ∈ { (AC1GsGiCaMCa4ATP, AC1GsaGTPGiaGTPCaMCa4), | _memb) } | ||||||
(AC8CaMCa4ATP, AC8CaMCa4) } | (, ) ∈ { (_S845_S831, _S845_S831_PP1), (_S831, | ||||||
(, ) ∈ { (CaMCa2, CaMCa3), (PP2BCaMCa2, | _S831_PP1), (_memb_S845_S831, _memb_S845_S831_PP1), | ||||||
PP2BCaMCa3) } | (_memb_S831, _memb_S831_PP1) } | ||||||
(, ) ∈ { (CaMCa3, CaMCa4), (PP2BCaMCa3, | (, ) ∈ { (_S845_S831_PP1, _S845), (_S845_S831_PP1, | ||||||
PP2BCaMCa4) } | _S831), (_S831_PP1, ), (_memb_S845_S831_PP1, _memb_S845), | ||||||
(, ) ∈ { (2, CaMCa2), (4, CaMCa4) } | (_memb_S845_S831_PP1, _memb_S831), (_memb_S831_PP1, | ||||||
∈ {pCaMCa4, CaMCa4} | _memb) } | ||||||
(, ) ∈ { (, PP1), (CaMCa4, CaMCa4PP1) } | (, ) ∈ { (_S845, _S845_PP2B), (_S845_S831, | ||||||
(, ) ∈ { (PP1, ), (CaMCa4PP1, CaMCa4) } | _S845_S831_PP2B), (_memb_S845, _memb_S845_PP2B), | ||||||
(, ) ∈ { (, CaMCa4), (PP1, P2BCaMCa4) } | (_memb_S845_S831, _memb_S845_S831_PP2B) } | ||||||
∈ {CaMCa4, P2BCaMCa4} | (, ) ∈ { (_S845_PP2B, ), (_S845_S831_PP2B, | ||||||
(, ) ∈ { (, _PKAc), (_memb, _memb_PKAc) } | _S831), (_memb_S845_PP2B, _memb), (_memb_S845_S831_PP2B, | ||||||
(, ) ∈ { (_PKAc, _S845), (_S831_PKAc, _S845_S831), | _memb_S831) } | ||||||
(_memb_PKAc, _memb_S845), (_memb_S831_PKAc, | ∈ {, _PKAc, _CKCam, _CKpCam, _CKp, _PKCt, _PKCp, | ||||||
_memb_S845_S831) } | _S831, _S831_PKAc, _S831_PP1} | ||||||
(, , ) ∈ { (, CaMCa4, _CKCam), (, p, | ∈ {, _CKCam, _CKpCam, _CKp, _PKCt, _PKCp, _S831, | ||||||
_CKp), (_S845, CaMCa4, _S845_CKCam), (_S845, p, _S845_CKp), | _PP1, _S831_PP1, _PP2B, _S831_PP2B} | ||||||
(_memb, CaMCa4, _memb_CKCam), (_memb, p, _memb_CKp), | (, , ) ∈ { (PKAc, PDE4, PDE4), (PDE4cAMP, PKAc, | ||||||
(_memb_S845, CaMCa4, _memb_S845_CKCam), (_memb_S845, p, | _PDE4_cAMP) } | ||||||
_memb_S845_CKp) } | (, ) ∈ { (PDE4, ), (_PDE4_cAMP, cAMP) } | ||||||
(, , ) ∈ { (_CKCam, _S831, CaMCa4), (_CKp, _S831, | (, ) ∈ { (GqaGTP, ), (CaGqaGTP, Ca) } | ||||||
p), (_S845_CKCam, _S845_S831, CaMCa4), (_S845_CKp, _S845_S831, | (, , ) ∈ { (, t, _PKCt), (, p, _PKCp), | ||||||
p), (_memb_CKCam, _memb_S831, CaMCa4), (_memb_CKp, _memb_S831, | (_memb, t, _memb_PKCt), (_memb, p, _memb_PKCp) } | ||||||
p), (_memb_S845_CKCam, _memb_S845_S831, CaMCa4), | (, , ) ∈ { (_PKCt, _S880, t), (_PKCp, _S880, p), | ||||||
(_memb_S845_CKp, _memb_S845_S831, p) } | (_memb_PKCt, _memb_S880, t), (_memb_PKCp, _memb_S880, p) } | ||||||
(, , ) ∈ { (, CKpCaMCa4, _CKpCam), (, | (, ) ∈ { (_S880, _S880_PP2A), (_memb_S880, | ||||||
PKCt, _PKCt), (, PKCp, _PKCp), (_S845, CKpCaMCa4, | _memb_S880_PP2A) } | ||||||
_S845_CKpCam), (_S845, PKCt, _S845_PKCt), (_S845, PKCp, | (, ) ∈ { (_S880_PP2A, ), (_memb_S880_PP2A, | ||||||
_S845_PKCp), (_memb, CKpCaMCa4, _memb_CKpCam), (_memb, PKCt, | _memb) } | ||||||
_memb_PKCt), (_memb, PKCp, _memb_PKCp), (_memb_S845, CKpCaMCa4, | ∈ {, _PKCt, _PKCp} | ||||||
_memb_S845_CKpCam), (_memb_S845, PKCt, _memb_S845_PKCt), | ∈ {, _PP2A} | ||||||
(_memb_S845, PKCp, _memb_S845_PKCp) } |
All non-mentioned species have an initial concentration of 0 nM.
Species | Conc. (nM) | Species | Conc. (nM) | Species | Conc. (nM) | |||
---|---|---|---|---|---|---|---|---|
CaOut | extracell. Ca2+ | 1900000 | AMP | adenosine monophosphate | 980 | Pip2 | phosphatidylinositol 4,5-bisphosphate | 24000 |
Leak | leak channels | 2000 | Ng | neurogranin | 20000 | PIkinase | phosphatidylinositol kinase | 290 |
Calbin | calbindin | 150000 | CaM | calmodulin | 60000 | Ip3degPIk | Ip3-bound PI kinase | 400 |
CalbinC | Ca2+-bound calbindin | 15000 | PP2B | protein phosphatase 2B | 2300 | PKC | protein kinase C | 15000 |
LOut | extracell. β-adr. ligand | 2500000 | CK | CaMKII | 23000 | DAG | diacylglycerol | 90 |
Epac1 | Epac1 | 500 | PKA | protein kinase A | 6400 | DAGK | DAG kinase | 300 |
PMCA | Ca2+ pump | 22000 | I1 | inhibitor-1 | 2200 | DGL | DAG lipase | 1600 |
NCX | Ca2+ exchanger | 540000 | PP1 | protein phosphatase 1 | 1600 | CaDGL | Ca2+-bound DAG lipase | 250 |
L | β-adrenergic ligand | 10 | GluR1 | AMPAR subunit type 1 | 180 | DAGCaDGL | Ca2+-and DAG-bound DAG lipase | 90 |
R | β-adrenergic receptor | 1600 | GluR1_memb | membrane-inserted GluR1 | 90 | Ip3degrad | degraded Ip3 | 600 |
Gs | S-type G-protein | 13000 | PDE4 | phosphodiesterase type 4 | 670 | GluR2 | AMPAR subunit type 2 | 14 |
Gi | I-type G-protein | 2600 | fixedbuffer | immobile buffer | 500000 | GluR2_memb | membrane-inserted GluR2 | 256 |
AC1 | adenylyl cyclase type 1 | 430.0 | mGluR | metab. glutamate receptor | 800 | PP2A | protein phosphatase 2A | 500 |
ATP | adenosine triphosphate | 2000000 | GluOut | extracell. glutamate | 1000000 | M1R | acetylcholine receptor M1 | 450 |
AC8 | adenylyl cyclase type 8 | 370 | Gqabg | Q-type G-protein | 1400 | PLA2 | phospholipase A2 | 1000 |
PDE1 | phosphodiesterase type 1 | 12000 | PLC | phospholipase C | 250 |