Loose coupling between Ca2+ channels and release sensors as a synaptic correlate of higher-order brain function
- Carl Ludwig Institute for Physiology, Medical Faculty, University of Leipzig, Germany
Figures
Figure 1 with 2 supplements
Differences in synaptic transmission and plasticity between prefrontal cortex (PFC) and primary somatosensory cortex (S1) synapses.
(A) Schematic representation of the mature mouse brain (top) and the positions at which coronal sections were made from PFC (orange; middle) or S1 (blue; bottom). Recordings were made in acute slices from layer 5 pyramidal neuron (L5PN)-L5PN pairs or from L2/3-L5PN connections. (B) EPSCs (bottom) recorded from postsynaptic L5PNs after evoking action currents in the presynaptic L5PNs (top, inset: threefold magnification) in PFC (left) or S1 (right), individual recordings in gray, averages in black. (C–F) Summary of basic synaptic properties: EPSC amplitudes (C), failure rates (D), synaptic delays (E), and their SD values (F) in PFC and S1 (medians ± IQRs, means as dashed lines, whiskers represent 10th and 90th percentiles, dots indicate outliers, numbers of cell pairs in brackets; ***p<0.001, Mann-Whitney U test [MWU]). Data from S1 are from Bornschein et al., 2019a. (G) EPSCs recorded from pairs of L5PNs at 50 Hz intervals in PFC (top) and S1 (bottom), presynaptic stimulations are omitted, averages from at least 10 individual recordings. (H, I) Summary of paired pulse ratios (PPRs) (H; ***p<0.001, MWU) and success rates (I) following the 1st (1_x) and second stimulation (x_1; ***p<0.001, p=0.987, Wilcoxon signed-rank test [WSR]). S1 data are from Bornschein et al., 2019b. (J) As in (G) but for L2/3-L5 synapses (bottom, averages from at least 15 individual recordings, stimulation artifacts were blanked for clarity, arrowheads denote the time points of extracellular stimulation). (K) Boxplots summarizing PPR data from lateral PFC (PFC), medial PFC (mPFC), older PFC (P90–100), and S1 (***p<0.001, n.s., not significant, ANOVA on ranks). (L) Comparison of SDs of the synaptic delays at L2/3-L5 synapses between PFC and S1 (***p<0.001, MWU).
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Figure 1—source data 1
Data from recordings of L5PN-L5PN connections corresponding to Figure 1B-I.
- https://cdn.elifesciences.org/articles/110314/elife-110314-fig1-data1-v1.xlsx
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Figure 1—source data 2
Data from recordings of L2/3-L5PN connections corresponding to Figure 1J-L.
- https://cdn.elifesciences.org/articles/110314/elife-110314-fig1-data2-v1.xlsx
Figure 1—figure supplement 1
Short-term plasticity in prefrontal cortex (PFC) and primary somatosensory cortex (S1).
(A) EPSCs recorded from a layer 5 pyramidal neuron (L5PN)-L5PN pair in PFC at interstimulus intervals (ISIs) ranging from 5 to 500 ms. (B) Comparison of paired pulse ratios (PPRs) recorded at different ISIs from pairs of L5PNs in PFC (orange) and S1 (blue). Averages shown as medians and interquartile ranges (IQRs) (n in brackets; p=0.104, **p=0.008, ***p<0.001, Mann-Whitney U test [MWU]). S1 data are from Bornschein et al., 2019b. (C) Same as in (A), but for recordings from prefrontal L5PNs after extracellular stimulation in L2/3 with paired pulses at ISIs of 10 to 500 ms. (D) Same as in (B), but for L2/3-L5PN synapses in PFC and S1 (***p<0.001, MWU).
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Figure 1—figure supplement 1—source data 1
Data from recordings of L5PN-L5PN connections corresponding to Figure 1—figure supplement 1B.
- https://cdn.elifesciences.org/articles/110314/elife-110314-fig1-figsupp1-data1-v1.xlsx
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Figure 1—figure supplement 1—source data 2
Data from recordings of L2/3-L5PN connections corresponding to Figure 1—figure supplement 1D.
- https://cdn.elifesciences.org/articles/110314/elife-110314-fig1-figsupp1-data2-v1.xlsx
Figure 1—figure supplement 2
Different NMDA receptor contributions in prefrontal cortex (PFC) and primary somatosensory cortex (S1).
(A) Examples of EPSCs recorded from L2/3-layer 5 pyramidal neuron (L5PN) connections in PFC and S1. (B) Summary of EPSC decay time constants (τdecay) in PFC and S1 (**p=0.002, Mann-Whitney U test [MWU]). (C) Top: Averaged example recordings before (baseline in black) and after application of 50 μM 2-amino-5-phosphonovaleric acid (APV) in PFC (orange) and S1 (blue). Bottom: EPSC recordings from top graphs normalized to baseline emphasizing changes in synaptic decay. (D–F) Box plots comparing normalized EPSC amplitudes (D; *p=0.031, p=1.0, Wilcoxon signed-rank test [WSR]), their charges (E; *p=0.016, MWU), and τdecay values in the presence of 50 µM APV (F; p=0.329) in PFC and S1.
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Figure 1—figure supplement 2—source data 1
Data from recordings of L2/3-L5PN connections corresponding to Figure 1—figure supplement 2B-F.
- https://cdn.elifesciences.org/articles/110314/elife-110314-fig1-figsupp2-data1-v1.xlsx
Figure 2 with 1 supplement
Area-specific differences in EGTA sensitivity.
(A) Averaged, baseline-normalized EPSC amplitudes (means ± SEMs, 2 min bins) recorded from layer 5 pyramidal neuron (L5PN)-L5PN pairs in prefrontal cortex (PFC) with standard pipette solution (control, orange) and after re-patching the presynaptic neuron with a pipette solution containing 10 mM EGTA (blue). Insets: Average EPSCs from one pair during baseline (−10 to 0 min) and test period (20–30 min) for control and EGTA (averages normalized to baseline). (B) Boxplot comparing the normalized EPSC amplitudes prior to and following the application of EGTA and/or BAPTA with control recordings in L5PN pairs in PFC (*p=0.041, Mann-Whitney U test [MWU]) and primary somatosensory cortex (S1) (***p<0.001, p=0.365, one-way ANOVA; Shapiro-Wilk normality test: p=0.597). S1 data are from Bornschein et al., 2019a. Note the significant EGTA effect. (C) As in (A) but for L2/3-L5PN connections in PFC. Following baseline recordings (10 min), slices were perfused for 30 min (solid line) with artificial cerebrospinal fluid (ACSF) containing either 10 μM EGTA-AM (blue), 10 μM BAPTA-AM (red), or only the solvent DMSO/Pluronic (control, orange), and thereafter rinsed for 10 min with ACSF (test period). Insets: Averaged EPSCs during baseline and test period. (D) Summary of chelator-AM effects in PFC, medial PFC (mPFC), and older PFC (P90–100; ***p<0.001, **p=0.009, *p=0.032, one-way ANOVA vs. control; Shapiro-Wilk normality test: p=0.666). Note the similar EGTA sensitivity of release in all PFC recordings (p=0.347, one-way ANOVA). (E) As in (C) but for L2/3-L5PN connections in S1 (control in light blue). (F) Summary of chelator-AM effects in S1 (**p=0.006, ANOVA on ranks). Note the absence of a significant EGTA effect in S1 (p=0.943, MWU).
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Figure 2—source data 1
Data from recordings of L5PN-L5PN connections corresponding to Figure 2A and B.
- https://cdn.elifesciences.org/articles/110314/elife-110314-fig2-data1-v1.xlsx
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Figure 2—source data 2
Data from recordings of L2/3-L5PN connections corresponding to Figure 2C-F, Figure 2—figure supplement 1.
- https://cdn.elifesciences.org/articles/110314/elife-110314-fig2-data2-v1.xlsx
Figure 2—figure supplement 1
EGTA sensitivity in prefrontal cortex (PFC).
(A, B) Example recording of baseline-normalized EPSC amplitudes (means ± SDs, 20 EPSCs each were binned) recorded from an L2/3-layer 5 pyramidal neuron (L5PN) connection in PFC (A) and primary somatosensory cortex (S1) cortex (B) derived from the same mouse (P24). Following baseline recordings (10 min), slices were perfused for 30 min (solid line) with artificial cerebrospinal fluid (ACSF) containing 10 μM EGTA-AM (blue), and thereafter rinsed for 10 min with ACSF (test period). Insets: EPSCs (averages in blue, individual recordings in gray) during baseline and test period. (C) Boxplot summarizing EGTA-AM effects in PFC and S1. Individual experiments are included as data points; data obtained from the same mouse were connected by a line. Note the significant EGTA sensitivity in PFC (**p=0.002, Mann-Whitney U test [MWU]). (D) Averaged, baseline-normalized EPSCs (2 min bins) recorded from L2/3-L5PN connections in PFC of 90- to 100-day-old mice as in Figure 2C. Insets: Averaged EPSCs during baseline and test period. (E) Same as in (D), but for L2/3-L5PN connections in medial PFC (mPFC) of 21- to 26-day-old mice .
Figure 3
Quantal synaptic parameters in prefrontal cortex (PFC) and primary somatosensory cortex (S1).
(A) Multiple probability fluctuation analysis (MPFA) of EPSC amplitudes recorded at the indicated [Ca2+]e from a pair of layer 5 pyramidal neurons (L5PNs) in PFC. Top: EPSCs (gray, average in black) recorded in 1, 2, and 5 mM [Ca2+]e. Middle: Plot of EPSC amplitudes over time. Bottom: Corresponding mean-variance plot fitted with a parabola estimating the quantal parameters of release. pN is for 2 mM [Ca2+]e. (B) As in (A), but for an L2/3-L5PN connection in PFC. Recordings were made in the presence of 0.25 mM kynurenic acid (Kyn) and 50 µM 2-amino-5-phosphonovaleric acid (APV). (C) As in (B), but in S1. (D) Summary of quantal release parameters in L5PN pairs from PFC and S1 and in S1 with 1–2 mM γ-DGG (γ-D-glutamylglycine) (S1 data from Bornschein et al., 2019a; p=0.121, *p=0.048, p=0.054, ANOVA on ranks). (E) Left: Example of evoked qEPSCs (top) and the corresponding amplitude histogram (bottom, gray range was used for calculating the qEPSC amplitude). Right: Summary of qEPSC amplitudes in PFC and S1 (**p=0.004, Mann-Whitney U test [MWU]). (F) Summary of pN values in L2/3-L5PN connections from PFC and S1 (p=0.485, MWU).
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Figure 3—source data 1
Data from recordings of L5PN-L5PN connections corresponding to Figure 3A, D and E.
- https://cdn.elifesciences.org/articles/110314/elife-110314-fig3-data1-v1.xlsx
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Figure 3—source data 2
Data from recordings of L2/3-L5PN connections corresponding to Figure 3B, C and F.
- https://cdn.elifesciences.org/articles/110314/elife-110314-fig3-data2-v1.xlsx
Figure 4 with 1 supplement
Presynaptic Ca2+ transients are similar in prefrontal cortex (PFC) and primary somatosensory cortex (S1).
(A) Two-photon images of layer 5 pyramidal neurons (L5PNs) in PFC (left) and S1 (right) filled with Fluo-5F and Alexa 594 (scale bar 50 µm). Insets: Magnifications showing presynaptic boutons from which Ca2+ transients are recorded (scale bar 5 µm). (B) G/R signals (top) evoked by single APs in individual cells (gray, average of 6–15 boutons each, grand average in black) and their conversion to Ca2+ increases (∆[Ca2+]i, bottom). (C–F) Summary of G/R signals (C; p=0.112, Mann-Whitney U test [MWU]; numbers of boutons and cells in brackets), ∆[Ca2+]i (D; p=0.361), decay time constants τ1 and τ2 (E; p=0.532, 0.962), and basal ∆[Ca2+]i (F; p=0.597) in PFC and S1. Note that there is no significant difference in presynaptic Ca2+ transients between PFC and S1.
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Figure 4—source data 1
Data from calcium imaging experiments in L5PN boutons corresponding to Figure 4C-F.
- https://cdn.elifesciences.org/articles/110314/elife-110314-fig4-data1-v1.xlsx
Figure 4—figure supplement 1
In vitro calibration curve and basal ∆[Ca2+]i.
(A) Calibration curve of Fluo-5F in a K-gluconate-based pipette solution. The KD value of 439 nM was derived from a Hill fit (solid curve). (B) Comparison of basal [Ca2+]i determined with Fluo-5F and OGB-1, respectively (p=0.204, Mann-Whitney U test [MWU]).
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Figure 4—figure supplement 1—source data 1
Data from calcium imaging experiments in L5PN boutons corresponding to Figure 4—figure supplement 1A.
- https://cdn.elifesciences.org/articles/110314/elife-110314-fig4-figsupp1-data1-v1.xlsx
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Figure 4—figure supplement 1—source data 2
Data from calcium imaging experiments in L5PN boutons corresponding to Figure 4—figure supplement 1B.
- https://cdn.elifesciences.org/articles/110314/elife-110314-fig4-figsupp1-data2-v1.xlsx
Figure 5 with 1 supplement
Model predicts microdomain coupling at prefrontal cortex (PFC) synapses.
(A) Fit of the model (blue line) to the measured average Ca2+ signal (A; gray line) of layer 5 pyramidal neuron (L5PN) boutons in PFC. The fit was obtained with the indicated number of open voltage-gated Ca2+ channels (VGCCs). (B) pN values were simulated with the Syt1 priming model (Bornschein et al., 2019a; Bornschein et al., 2025) for control conditions and in the presence of EGTA with different VGCC numbers yielded different coupling distances (CDs) in the model. The simulated pN were subtracted from and normalized to the experimental values, i.e., a value close to zero indicates best agreement between simulation and experiment. This was obtained with nine open VGCCs at a CD of 51 nm (see C). (C) Simulated pN for nine open VGCCs under control conditions at increasing CDs (blue line). The experimental pN value (median ± IQR, dashed line, gray range, Figure 3D) was reproduced at a CD of 51 nm (48–55 nm). (D) Illustration of the ring model used in B and C with a CD of 51 nm between nine VGCCs (orange) and the release sensor of a vesicle (blue). (E) Examples of averaged normalized paired pulse recordings at 50 Hz at L2/3-L5PN synapses before (black) and after (orange) application of 5 µM Cd2+ in PFC. (F) Bar graph quantifying normalized paired pulse ratios (PPRs) after Cd2+ application in PFC and primary somatosensory cortex (S1) (**p=0.005, p=0.667, paired t-test; Shapiro-Wilk normality test: p=0.514). Note that Cd2+ increased the PPR in PFC.
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Figure 5—source data 1
Data from recordings of L2/3-L5PN connections corresponding to Figure 5F.
- https://cdn.elifesciences.org/articles/110314/elife-110314-fig5-data1-v1.xlsx
Figure 5—figure supplement 1
Prediction of the coupling distance with an alternative Syt1 model.
As in Figure 5B but instead of the Syt1 priming model, the Syt1 model (Bornschein et al., 2019b; Bornschein et al., 2025) was used for simulating the release rates and the corresponding pN values.
Scheme 1
Syt1 priming model.
Scheme 2
Syt1 model.
Author response image 1
MPFA with four different extracellular Ca2+ concentrations.
(A) MPFA of EPSC amplitudes recorded at the indicated [Ca2+]e from L2/3-L5PNs in PFC. Top: Individual EPSCs (grey, average in black) recorded from L5PNs after extracellular stimulation in L2/3. Middle: Plot of EPSC amplitudes over time. Bottom: Corresponding mean-variance plot fitted with a parabola estimating the quantal parameters of release. pN is for 2 mM [Ca2+]e. Recordings were made in the presence of 10 µM Bicuculline, 0.25 mM Kynurenic acid and 50 µM 2-Amino-5-phosphonovaleriansäure. (B) As in (A), but for a L2/3-L5PN connection in S1. (C) Summary of determined pN values in PFC and S1 (dots represent individual experiments; P=0.485, Mann-Whitney U rank-sum test).
Author response image 2
Bootstrap analysis (A-C) Distribution of bootstrap 25% trimmed means of the quantal parameters pN (A), N (B) and q (C) in PFC (orange), S1 (blue) and S1 with gDGG (light blue).
10,000 bootstrap replicates were generated with replacement from the original data sample obtained by MPFA in L5PN-L5PN connections (cf. Figure 3D). (D) Same as in (A) but for MPFA in L2/3-L5PN connections.
Tables
Table 1
New and previously published data.
| Synapse/region | Experiments/analyses | Figures | Data |
|---|---|---|---|
| L5PN-L5PN PFC | EPSC amplitudes, failure rates, delays, SDDelay, PPRs, success rates | Figure 1B–I Figure 1—figure supplement 1A and B | This study |
| L5PN-L5PN S1 | EPSC amplitudes, failure rates; additional quantification of delays, SDDelays, PPRs, success rates | Figure 1B–I Figure 1—figure supplement 1B | Bornschein et al., 2019b; Bornschein et al., 2019a |
| L2/3-L5PN PFC and S1 | PPRs, SDDelay | Figure 1J–L Figure 1—figure supplement 1C and D | This study |
| L2/3-L5PN PFC and S1 | NMDA receptor contribution | Figure 1—figure supplement 2A–F | This study |
| L5PN-L5PN PFC | Chelator experiments, CD | Figure 2A and B | This study |
| L5PN-L5PN S1 | Chelator experiments, CD; Reanalyses of EGTA effects at 20–30 min test period | Figure 2B | Bornschein et al., 2019a |
| L2/3-L5PN PFC and S1 | Chelator experiments, CD | Figure 2C–F Figure 2—figure supplement 1A–E | This study |
| L5PN-L5PN PFC | MPFA | Figure 3A, D, and E | This study |
| L5PN-L5PN S1 | MPFA | Figure 3D and E | Bornschein et al., 2019a |
| L2/3-L5PN PFC and S1 | MPFA | Figure 3B, C, and F | This study |
| L5PN PFC | 2P Ca2+ imaging | Figure 4A–F | This study |
| L5PN S1 | 2P Ca2+ imaging | Figure 4A–F Figure 4—figure supplement 1A | This study |
| L5PN S1 | 2P Ca2+ imaging: basal [Ca2+]i with Fluo-5F and OGB-1 | Figure 4—figure supplement 1B | Bornschein et al., 2025; this study |
| L2/3PN and L5PN PFC | Modeling | Figure 5A–D Figure 5—figure supplement 1 | This study |
| L2/3-L5PN PFC | Cd2+ experiments | Figure 5E and F | This study |
| L2/3-L5PN PFC | Cd2+ experiments | Figure 5E and F | This study |
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Strain, strain background (Mus musculus, female/male) | C57BL/6J | Animal Facility, Medical Faculty, University of Leipzig | N/A | P21–26 and P90–100 |
| Chemical compound, drug | NaCl | Merck | Cat. # 1.06400.1000, RRID:SCR_001287 | |
| Chemical compound, drug | KCl | Sigma-Aldrich | Cat. # P9333, RRID:SCR_008988 | |
| Chemical compound, drug | NaH2PO4 | Merck | Cat. # 1.06349.1000, RRID:SCR_001287 | |
| Chemical compound, drug | NaHCO3 | Roth | Cat. # 6885.1, RRID:SCR_005711 | |
| Chemical compound, drug | MgCl2 | Sigma-Aldrich | Cat. # M2670, RRID:SCR_008988 | |
| Chemical compound, drug | CaCl2 | Sigma-Aldrich | Cat. # C5080, RRID:SCR_008988 | |
| Chemical compound, drug | Glucose | Roth | Cat. # 6780.1, RRID:SCR_005711 | |
| Chemical compound, drug | (-)-Bicuculline methiodide | Tocris | Cat. # 2503, RRID:SCR_003689 | |
| Chemical compound, drug | K-gluconate | Sigma-Aldrich | Cat. # G4500, RRID:SCR_008988 | |
| Chemical compound, drug | Na2ATP | Sigma-Aldrich | Cat. # A26209, RRID:SCR_008988 | |
| Chemical compound, drug | NaGTP | Sigma-Aldrich | Cat. # G8877, RRID:SCR_008988 | |
| Chemical compound, drug | EGTA | Sigma-Aldrich | Cat. # E0396, RRID:SCR_008988 | |
| Chemical compound, drug | KHEPES | Sigma-Aldrich | Cat. # H0527, RRID:SCR_008988 | |
| Chemical compound, drug | KOH | Roth | Cat. # K017.1, RRID:SCR_005711 | |
| Chemical compound, drug | HCl | Roth | Cat. # K024.1, RRID:SCR_005711 | |
| Chemical compound, drug | DMSO | Sigma-Aldrich | Cat. # D8418, RRID:SCR_008988 | |
| Chemical compound, drug | Pluronic F-127 | Molecular Probes | Cat. # P3000MP, RRID:SCR_013318 | |
| Chemical compound, drug | EGTA-AM | Invitrogen, Thermo Fisher | Cat. # E1219, RRID:SCR_008452 | |
| Chemical compound, drug | BAPTA-AM | Invitrogen, Thermo Fisher | Cat. # B6769, RRID:SCR_008452 | |
| Chemical compound, drug | CdCl2 | Sigma-Aldrich | Cat. # 655198, RRID:SCR_008988 | |
| Chemical compound, drug | 2-Amino-5-phosphonovaleric acid | Alomone labs | Cat. # D-145, RRID:SCR_013570 | |
| Chemical compound, drug | Kynurenic acid | Sigma-Aldrich | Cat. # K3375, RRID:SCR_008988 | |
| Chemical compound, drug | Fluo-5F | Invitrogen, Thermo Fisher | Cat. # F14221, RRID:SCR_008452 | |
| Chemical compound, drug | OGB-1 | Invitrogen, Thermo Fisher | Cat. # O6806, RRID:SCR_008452 | |
| Chemical compound, drug | Atto-594 | Atto-Tec, Sigma-Aldrich | Cat. # 05676, RRID:SCR_008988 | |
| Software, algorithm | MaxChelator | Stanford University | RRID:SCR_003210 | |
| Software, algorithm | Patchmaster version 2x90.2 | HEKA, Multichannel Systems | RRID:SCR_000034 | |
| Software, algorithm | Fluoview 300 version 4.3 | Olympus | RRID:SCR_020339 | |
| Software, algorithm | Mathematica 14 | Wolfram | RRID:SCR_014448 | |
| Software, algorithm | Igor Pro, version 6.32 and 8.03 | WaveMetrics | RRID:SCR_000325 | |
| Software, algorithm | Sigma Plot 11.0 | Dundas Software | RRID:SCR_003210 | |
| Other | Vibratome HM 650 V | Microm (Epredia), Fisher scientific | RRID:SCR_008452 | Slicing device |
| Other | Borosilicate glass | Hilgenberg | Cat. # 1403569 | Patch pipettes |
| Other | Puller PC-10 | Narishige | RRID:SCR_022057 | Pulling device |
| Other | Microscope BX51WI | Olympus | RRID:SCR_023069 | Imaging device |
| Other | Amplifier EPC10/2 | HEKA, Multichannel Systems | RRID:SCR_018399 | Electrophysiology device |
| Other | Stimulus Isolator ISO-Stim 01 DPI | NPI electronics | RRID:SCR_016002 | Electrophysiology device |
| Other | Fluoview-300 scanner | Olympus | RRID:SCR_020339 | Imaging device |
| Other | Tsunami Ti:sapphire laser | Newport-Spectra Physics | https://www.spectra-physics.com | Imaging device |
| Other | Pockels cell 350–80 KD*P | Conoptics | https://www.conoptics.com | Imaging device |
| Other | Filters HC647/75, Semrock HC525/50, 720-SP | AHF | https://ahf.de | Imaging device |
| Other | PMT module H7422-40 | Hamamatsu | https://www.hamamatsu.com RRID:SCR_017105 | Imaging device |
| Other | PMT module PMT-02M/PMM-03 | NPI electronics | RRID:SCR_016002 | Imaging device |
Table 2
Model parameters.
| Parameters | Values | References/notes | |
|---|---|---|---|
| Bouton volume | 0.13 * 10–15 l | Schikorski and Stevens, 1999* | |
| Calcium | [Ca2+]rest | 30*10–9 M | Measured |
| D | 220 *10–12 m2s–1 | Allbritton et al., 1992 | |
| Fluo-5F | [Fluo] | 140 *10–6 M | 70% of pipette concentration |
| KD | 439 *10–9 M | Measured | |
| koff | 300 s–1 | Scott and Rusakov, 2006 | |
| D | 220 *10–12 m2s–1 | 2† | |
| EGTA | KD | 7*10–8 M | Klicken Sie hier, um Text einzugeben (Nägerl et al., 2000) |
| koff | 0.7 s–1 | ibid. | |
| kon | 1*107 M–1s–1 | ibid. | |
| D | 220 *10–12 m2s–1 | Naraghi and Neher, 1997 | |
| ATP | [ATP] | 6 *10–4 M | Pipette concentration |
| KD | 2*10–4 M | Meinrenken et al., 2002 | |
| koff | 100 000 s–1 | ibid. | |
| kon | 5*108 M–1s–1 | ibid. | |
| D | 220 *10–12 m2s–1 | ibid. | |
| κ | 3 | Calculated | |
| Immobile endogenous Ca2+ buffer (EB) | κE | 25 | Tran and Stricker, 2018; Bornschein et al., 2019a |
| Fast EB | [EBf] | 46.5 *10–6 M | Calculated |
| KD | 2*10–6 M | Vyleta and Jonas, 2014; Bornschein et al., 2019a | |
| koff | 1000 s–1 | ibid. | |
| kon | 5*108 M–1s–1 | ibid. | |
| κE | 23.25 | Calculated | |
| Slow EB | [EBs] | 1.23*10–7 M | Calculated |
| KD | 7*10–8 M | Nägerl et al., 2000 | |
| koff | 0.7 s–1 | ibid. | |
| kon | 1*107 M–1s–1 | ibid. | |
| κE | 1.75 | Calculated | |
| P/Q-type channel | a, b | 247.71, 8.28 ms–1 | Li et al., 2007 |
| α1,0,β1,0 | 5.89, 14.99 ms–1 | ibid. | |
| α2,0, β2,0 | 9.21, 6.63 ms–1 | ibid. | |
| α3,0, β3,0 | 5.2, 132.8 ms–1 | ibid. | |
| α4,0,β4,0 | 1823.18, 248.58 ms–1 | ibid. | |
| k1 | 62.61 mV | ibid. | |
| k2 | 33.92 mV | ibid. | |
| k3 | 135.08 mV | ibid. | |
| k4 | 20.86 mV | ibid. | |
| Release sensor models | Bornschein et al., 2025 | ||
| Syt1 model | koff | 10 000 s–1 | ibid. |
| kon | 1*108 M–1s–1 | ibid. | |
| γ | 5900 s–1 | ibid. | |
| β | 4 | ibid. | |
| Syt1 priming model | koff | 10 000 s–1 | ibid. |
| kon | 1*108 M–1s–1 | ibid. | |
| γ | 4000 s–1 | ibid. | |
| β | 4 | ibid. | |
| KM | 20*10–6 M | ibid. | |
| kprim | 6000 s–1 | ibid. | |
| n | 5 | ibid. |
-
*
Corrected for the space occupied by vesicles and organelles (Wilhelm et al., 2014).
-
†
Assumed to be similar to free Ca2+ (Bucurenciu et al., 2008).
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Loose coupling between Ca2+ channels and release sensors as a synaptic correlate of higher-order brain function
eLife 15:RP110314.
https://doi.org/10.7554/eLife.110314.3
