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# pre_vgcc.md: Voltage-Controlled Gated Channels

## PRE_VGCC

Intro:
  - is expanded and tuned by: [PRESYNAPSE](presynapse.md)

Voltage-Controlled Gated Channels: Qui per ora non gestiamo l'evoluzione della depolarizzazione. Alla scomparsa dell'AP, i VGCC smettono di funzionare.

```Gen
PRE_VGCC
    type: comprehension

  expansion:

  intrication:
    # Scope
    !DAY: INTRICATION [ ref: &ORGANISM.!DAY ]
    !NIGHT: INTRICATION [ ref: &ORGANISM.!NIGHT ]
    
    # Context  
    *AP: INTRICATION [ ref: &SOMA.*AP ]
    
    # Tub
    _NT: INTRICATION [ ref: &ASTROSYNAPSE._NT ] 
    _Ca2: INTRICATION [ ref: &PRESYNAPSE._Ca2 ] 

  instantiation:
    # Behaviour
    @: BEHAVIOUR [ behaviour: MAIN_VGCC_PRE ]  
```

### MAIN_VGCC_PRE: !DAY

Voltage-Controlled Gated Channels: Qui per ora non gestiamo l'evoluzione della depolarizzazione. Alla scomparsa dell'AP, i VGCC smettono di funzionare.

```Gen
MAIN_VGCC_PRE
  type: behaviour

  within_scope: !DAY
  
  snippets:
    # *AP
    @: ACCUMULATOR [ snippet: Ca2enterLow, rf: active 12x ]
    @: ACCUMULATOR [ snippet: Ca2enterMedium, rf: active 6x ]
    @: ACCUMULATOR [ snippet: Ca2enterHigh, rf: active 3x ]

    # NOT *AP
    @: ACCUMULATOR [ snippet: Ca2ClearanceLow, rf: active 24x ]
    @: ACCUMULATOR [ snippet: Ca2ClearanceHigh, rf: active 4x ]
```

#### *AP

Da rivedere le condizioni per aggiungere mGluR che ha come proxy NT concentration!!!!!

Here we comprehend the breaking activity on VGCC by: CDI, eCB and mGluR:

![breaking-cases.png](.attachments/breaking-cases.png)

Qui semplifichiamo:

- Approssimiamo CDI con concentrazione di Ca2.
  \-- CDI is calcium-dependent inactivation of VGCCs. The inactivation happens because Ca2 enters through the channel and binds to a calmodulin tethered to the channel's intracellular face, physically blocking it from reopening. This is a local, channel-specific event — it requires Ca2 to be flowing through that channel right now, not residual Ca2 drifting in the cytosol between spikes.
  \-- The recovery, by contrast, should run every millisecond unconditionally — CDI de-inactivation is a continuous process that proceeds whenever Ca2 dissociates from calmodulin, which depends on the ambient Ca_micro level at all times.
- Approssimiamo mGluR con concentrazione NT
- **Open** — zero active brakes. mGluR alone never escapes this group because its ceiling is alpha_mGluR = 0.4, meaning even at full it only removes 40% of conductance, leaving 60% — still above the 85% threshold. So mGluR is irrelevant to the open/not-open boundary. Only CDI and eCB decide.
- **Reduced/partial** — exactly one meaningful brake active. Either CDI has started building (mediumness), or eCB has risen from sustained postsynaptic activity, but not both simultaneously. The system is aware something is happening but has not compounded yet. This is the normal operating range during moderate sustained firing.
- **Suppressed** — two brakes multiplying. The compounding is what defines this zone — no single variable alone produces it (except CDI approaching full). 0.5 × 0.5 = 0.25 remaining is where the synapse starts losing significant transmission efficacy. Biologically this is the pre-silence warning zone: CDI is building from residual Ca2 while eCB is already engaged from postsynaptic activity.
- **Closed — CDI** = full is the only reliable hard rule. Because CDI can reach 1.0 and appears as (1 - CDI_factor) in the formula, it alone drives conductance to zero regardless of eCB and mGluR state. The three-brake overlap corner case (eCB=full + CDI=mediumness + mGluR=full) also reaches here, but in practice CDI reaching full is the primary biological mechanism.

Devo controllare che le condizioni sotto siano esaustive. Qui ho confuso high con low, e inoltre ho messo NT per mGluR che devo controllare che abbia senso.

##### Ca2enterLow

```Gen
Ca2enterLow
    type: accumulator

    in_context: *AP

    hypothesis: _Ca2 empty AND _eCB empty
      action: [ _Ca2 increase, _ATP decrease ]
      trace: None
```

##### Ca2enterMedium

```Gen
Ca2enterMedium
    type: accumulator

    in_context: *AP

    hypothesis: _Ca2 mediumness OR 
                ( _eCB mediumness AND _Ca2 empty ) OR 
                ( _eCB full AND _Ca2 empty AND _NT empty )
      action: [ _Ca2 increase, _ATP decrease ]
      trace: None
```

##### Ca2enterHigh

```Gen
Ca2enterHigh
    type: accumulator

    in_context: *AP

    hypothesis: ( _Ca2 mediumness AND _eCB full ) OR 
                _eCB mediumness
      action: [ _Ca2 increase, _ATP decrease ]
      trace: None
```

#### NOT *AP

Qui eliminiamo Ca2. Il tempo che ci mette ad eliminare il Ca2 dovrebbe essere minoe dell'inervallo fra un *AP e un'altra. Siccome non comprendiamo per ora \_ATP, non c'e' accumulo di Ca2 per mancanza di \_ATP (stanchezza).

Non non comprendiamo anche il ristabilimento del Voltage, con altri Ioni entranti e uscenti, per ora tutto dipende da AP del SOMA. Non comprendiamo per ora:

- PMCA: primary, ATP-dependent
- NCX: fast, NOT ATP-dependent
- SERCA: slowest, ATP-dependent

Qui disinguiamo:

- Ca+2 fullness che si puo' verificare alla fine di un AP
- NOT Ca2 fullness che svuota piu' lentamente
- da capire se serve veramente questa distinzione per il tempo di svuotamento.

##### Ca2ClearanceLow

```Gen
Ca2ClearanceLow
    type: accumulator

    in_context: NOT *AP

    hypothesis: NOT _Ca2 fullness AND NOT _Ca2 empty 
      action: [ _Ca2 decrease ]
      trace: None
```

##### Ca2ClearanceHigh

```Gen
Ca2ClearanceHigh
    type: accumulator

    in_context: NOT *AP

    hypothesis: NOT _Ca2 empty
      action: [Ca2 decrease]
      trace: None
```
