Electrical vs chemical synapses

Where electrical synapses found

• between neurons

• between glial cells

Electrical synapses characterised by

• cytoplasmic continuity between presynaptic and postsynapatic cell

How is this continuity facilitated by

Gap junction channels

• two connexons

  • each made of 6 connexins

  • so one gap junction→ 12 connexins

    • diverse group of trans membrane proteins

    • have many types and different genes

• each embedded in membrane of pre and post cell

Structure of pore

• form large non specific pore

  • allows:

    • current, small peptides and anions and cations through

• So can be bidirectional

However, due to diverse range of connexins

• some are only unidirectional

Can close in response to

1. low pH

2. high Ca2+

3. phosphorylation

4. voltage

but depends on gap junction

Speed

• no delay

• due to it being continuous

• instantaneous

Firing can be instantaneous→ e.g cardiac muslce

• intercalated discs→ contain gap junctions

• negligible delay means a signal that splits to go through multiple gap junctions can travel through at the same time

  • Synchronised

  • can be very beneficial, depending on the need of the body

Chemical synapses

• no continuity

• cleft is 5-10x larger than electrical synapse

• unidirectional

• delay→ 1ms (very noticeable compared to electrical)

Why study the Neuromuscular junction to study synapses?

1. Size

   1. Micrometer scale at the NMJ

   2. vs nm scale in the brain

2. Simplicity

   1. our neutrotransmitter : one receptor system

   2. vs way more complicated systems in the brain

3. Accessibility

   1. do not need to damage strucutre

THEREFORE: ideal for electrophysiologyical recordings

Neuromuscular junction features

• myelinated motor neurone

  • wrapped in schwann cells

• synaptic bouton→ site of transmission

  • also covered in scwann cells

  • form the endplate

• on the muscle fibres

How is ACh packaged into vesicles

1. Choline into cell via symporter with Na+

2. acetyl-CoA made from glucose in mitochdonria

3. choline + acetyl-CoA → acetylcholine (ACh) using acetyltransferase (ChAT)

4. Vescicle proton pump H+ export

5. ACh into vescile through H+ symporter

Receptor for ACh in neuromuscular junction

• Nicotinic acetylcholine receptor (nAChR)

Nicotinic acetylcholine receptor (nAChR) features

• pentameric ionotropic channel

• 2 alpha/beta/delta/gamma NMJ

  • CNS ones have different: 2alpha/3beta

• Binding sites found between

  • two alpha subunits

  • neighbouring beta and delta subunits

How is the channel opened

• two binding sites must have ACh

What happens when open

• Na+ in

• K+ out

  • can both flow due to large pore size

• Ca2+ can also get through

• channel is non selective

Why called nicotinic

• nicotine can open it

• it is an agonist

Antagonists

• alpha-bungarotoxin

• curare

• bind and do not open it

Strucutre of post-synaptic→ end plate

• invaginations→ increase SA

• more nicontic receptors at the crests

• sodium voltage gated in the trophs