Cholinergic Neurotransmission Flashcards
What is cholinergic neurotransmission?
Involved in PNS and CNS
* Role in movt (muscle cont)
* Role in attention, learning and memory
- Inv in direct control of skeletal muscle tension mediated by ACh at NMJ
- Modulation of timing and tension in cardiac+smooth muscle mediated by ACh rel by postganglionic paraymp neurons
What are the 2 classes of cholinergic receptors?
- Nicotinic (nAChR)
- Muscarinic (mAChR)
What are common processes of Cholinergic neurotransmission?
- Synthesis storage, rel and Bdown of ACh
- Binding of transmitters by postsyn receptors and their sub subsequent activation
What are Nicotinic receptor subtypes?
- 11 identified
- Made up of 5 units
- All pentamers contain at least 2 a subunits whcih each bind at least 1 molecule of ACh
- Muscle-types receptors
- Neuronal subtypes
What are muscle-type receptors?
(Nicotinic subtype)
- At NMJ (N1 or Nm)
1. Embryonic form
2. Adult form
What are Neuronal-type receptors?
(Nicotinic subtype)
- Combo of 12 dif nicotinic receptor subtypes
- Homoeric
- Heteromeric
What are Muscarinic receptor subtypes?
- 5 subtypes (M1-M5)
* All found in CNS
* M1-M4 also found in other tissues - Part of large family of G-protein coupled receptors
* Use an intracellular secondary messenger system to transmit signals inside cells
Describe the distribution of cholinergic receptors
What is parasympathetic cholinergic innervation?
2 sets of neurons in PNS
- Preganglionic Neurons
* Cell bodies in brain and spinal cord
* Synapses on neuron in auto ganglio located near or in effector organs - Postsynaptic neurons
* Cell bodies in ganglion
* Synapses on effector
Can stim or inhib muscle contr dep on receptor
Explain the neuromuscular junction
- One neuron makes synapses with several fibres (A motor unit)
- AP release ACh and activates nicotinic receptors on muscle fibre
- Focal innervation = 1 synapse per muscle fibre - Innervation from 1 motor unit only
- Safety factor - Release 8-10X more ACh than required in order to always get muscle contraction when stimulation
Explain ACh synthesis
- ACh is catlysed by the enzyme choline acetyltransferase (ChAT)
- ChAT transfers the acetyl group from Acetyl CoA to choline, forming Acetylcholine
- ACh synth from dietary precursors:
1. Choline: In egg yolks, liver, fish, grains, nuts, soya
2. Acetyl-CoA: From Bdown of glucose
Expalin ACh recycling and re-synthesis
- ACh can’t be transported back into the neuron
* Broken down in synaptic cleft by enzyme acetylcholinesterase
* Produces choline and acetic acid - Choline is taken back into presyn cholinergic nerve terminal by energy dep co-transport with Na+
- Choline reuptake is rate lim step in ACh synth
- ACh synth
* In neuro cytosol
* By enzyme choline acetyltransferase
* Combines choline with acetyl coenzyme A derived from mitochondria and Krebs cycle
Expalin ACh recycling and re-synthesis 2
Diagram
What is the anatomy of brain cholinergic pathways?
Important for cognition - Medial Septal Group
Important for motor function - Pontine Cholinergic System
How does ACh effect cognitive performance?
- ACh depletion contributes to normal age-related cognitive decline
