lecture 01: NT release

what types of NT release exist?

spontaneous

asynchronous

Ca2+ independent

synchronous

describe each type of NT release, with respect to their AP & Ca2+ dependence

**spontaneous**: no AP involved, Ca2+ dependent

**asynchronous:** AP may be involved, but not in time w NT release; Ca2+ dependent

**Ca2+ independent:** no Ca2+ req, ATP is involved (opposite of spontaneous (e.g. reverse transport))

**synchronous:** AP & Ca2+ dependent

which type of NT release is most powerful & common in neurons?

synchronous

what 6 sets of electrochem/biochem events does synchronous NT release req?

1. presynaptic depolarisation
2. Ca2+ entry
3. vesicle moving + priming
4. vesicle docking
5. vesicle fusion
6. vesicle recycling

describe presynaptic depolarisation

1. axon hillock w lots of v-gated Na+ channels allows for AP to be produced
2. EPSPs are generated by +ve ions flowing into cell, and IPSPs by Cl- or GABA

describe Ca2+ entry

1. via depolarisation and AP, v-gated Ca2+ channels open, Ca2+ flows INTO terminal, and Ca2+ signal is produced to trigger exocytosis of synaptic vesicle contents
2. we want an __influx of Ca2+ entry for LONG AP__
3. Ca2+ is crucial for synchronous NT release; channels fall into 3 major families

how can synchronous NT release be regulated by presynaptic **receptors** (LGICs + GPCRs)?

**GPCRs coupled w Go:** when AP comes down, less likely to open GPCR

**LGIC** (Ca+ permeant): if Ca2+ enters, can __increase__ amount of Ca2+ entering cell

what are the 3 families of Ca2+ channels and their respective actions ?

1. CaV1: contraction, release, NT release
2. CaV2: NT release
3. CaV3: pacemaker

describe vesicle moving + priming

* priming involves the steps BEFORE docking/fusion, including the

a. movement of vesicle twds docking sites (**positional** priming)
b. molecular changes that allow Docking + fusion (**molecular** priming)

describe vesicle docking

* uses **SNARE** proteins
* SNARE proteins on vesicle membrane, and SNAPs on pre-synaptic memb have a SNARE motif which allows SNARE proteins to function when they dock

describe vesicle fusion (3 molecules involved?)

* uses **STY-1 proteins**
* once vesicle is docked, for fusion, must wait for STY-1, **Ca2+, and PIP2** to allow membranes to fuse together for __OPEN channel to form__ (open channel then allows NT to pass thru)

describe vesicle recycling (which protein is important?)

* once vesicle is fused & the NT is released in synaptic cleft, vesicle can be recycled
* vesicle gets mobilised back, remade into vesicle, and __**synaptobrevin**__ is reinserted using __**vesicular transporter**__ to fill vesicle back up w NT
* once filled back up, can repeat process

by which methods can synchronous NT release use 2+ NTs at the SAME synapse?

co-release & segregation

describe the process of co-release

2 NTs released from __same__ nerve terminal; mixture of both in vesicles.

* NAd + 5-HT in pineal gland
* ATP + NAd in symp vas deferens
* NAd + somtostatin in symp nerves

describe segregation

same axon with 2 terminals; 1 presynaptic terminal ONLY relates ONE NT, and the other releases another

T/F: Ca2+ entry is graded

true; its is NOT all or nothing