Cholinergic signalling (done) Flashcards
Which NS is ACh found in?
Both PNS & CNS
What are the main roles of ACh?
- Major function in movement (muscle contraction in PNS, motor control in CNS)
- Roles in attention, learning & memory
What does ACh do at the NMJ?
ACh mediates direct control of skeletal muscle tension at NMJ
(Modulation of timing & tension in the cardiac & smooth muscle mediated by ACh released by postganglionic parasympathetic neurons
What are the 2 classes of cholinergic receptors?
- Nicotinic (nAChR)
- Muscarinic (mAChR)
Who discovered ACh & how?
Otto Loewi (1921)
Used 2 frog hearts & stimulated the vagus nerve - HR slowed down, he realised vagus nerve must be releasing signals onto heart
Found vagus nerve was supplying chemical substances to organs = ACh
Who were the 2 guys involved in discovering ACh?
Henry Dale & Otto Loewi
How many clusters of cholinergic projections are there?
8 clusters
What are cholinergic projection neuron clusters (Ch)1-4 called?
Medial Septal Group
What is the Medial Septal Group?
Ch1-4 in the basal forebrain target cortical & limbic structures (attention, learning, memory)
What are cholinergic projection neuron clusters (Ch)5-6 called?
Pontine Cholinergic System
What is the Pontine Cholinergic System?
Ch5-6 in the caudal midbrain target the thalamus, midbrain & cerebellum (sleep, arousal & motor function)
What are Ch7-8 cholinergic projections?
In the midbrain target the brainstem & midbrain (motor/sensory function)
What are the 2 sets of neurons in the PNS?
- Preganglionic neurons
- Postganglionic/postsynaptic neurons
What are preganglionic neurons?
- Cell bodies in the brain & spinal cord (CNS)
- Synapses on neurons in an autonomic ganglion located near or in effector organs
What are postganglionic/postsynaptic neurons?
- Cell bodies in the ganglion
- Synapses on the effector
What is a ganglion?
Collection of PNS neuron cell bodies
What can the neurons in the PNS do depending on receptors?
Can stimulate or inhibit muscle contrations depending on receptors
What is ACh synthesis catalysed by?
By the enzyme choline acetyltransferase (ChAT)
What does ChAT (choline acetlytransferase) do to make ACh?
Transfers the acetyle group (CH3CO-) from acetyl-Coenzyme A (Acetyl-CoA) to choline
Forming ACh
What is ACh synthesised from?
From dietary precursors
What are the dietary precursors that make choline?
- Egg yolks
- Liver
- Fish
- Grains
- Nuts
- Soya
What are the dietary precursors that make acetyl-CoA?
From breakdown fo glucose
What are the 6 stages of synaptic ACh synthesis, release & recycling? (Short version)
1 - Synthesis
2 - Storage
3 - Release
4 - Effect
5 - Recycling
6 - Reuptake
What are the 6 stages of synaptic ACh synthesis, release & recycling? (Long version)
1 - Synthesis = Cytosolic choline acetlytransferase (ChAT) synthesis ACh
2 - Storage = Vesicular ChT loads ~10,000 ACh molecules into each 40-50nm vesicle
3 - Release = Action potential causes Ca2+ –> mediated vesicular release (~300 vesicles/AP)
4 - Effect = ACh diffuses across the synapse & activates post-synatic recpetors (EPSP, ~2ms)
5 - Recycling = ACh is metabolised to choline + acetate by acetylcholine esterase (AChE)
6 - Reuptake = ~80% of choline is taken up by presynaptic cell for resynthesis (Na+ dependent channel)
What is a motor unit at the NMJ?
Single motor neurone & all muscle fibres innervated
(Each motor unit functions as an individual unit)
What is focal innervation?
1 synapse per muscle fibre = innervation from 1 motor unit only
What is the safety factor at the NMJ?
8-10x the amount of ACh required is released
This means = 100% sucess rate of muscle contraction when a motorneurone fires
Where does muscle innervation come from in the SC?
The anterior ventral horn
What is the process of a signal reaching the NMJ?
–> Cell bodies in anterior ventral horn of SC
–> Signal goes to motor neurons (Alpha motor neurons)
–> Goes to innervate musce fibres at the NMJ –> by activating Nicotinic receptors on muscle fibre
Refer to slide 3.4 for diagram of NMJ
:)
What are the 3 stags of ACh recycling & resynthesis?
1 - Degredation
2 - Reuptake
3 - Resynthesis