Autonomic Nervous System Flashcards
Describe the process of Cholinergic Transmission.
- Action potential approaches synapse
- Voltage sensitive Ca2+ channels open
- Ca2+ stimulates ACh vesicle fusion
- ACh released into synapsefrom vesicles
- ACh activates postsynaptic receptor
- ACh broken down by AChE into acetate and choline.
Describe the structure of Nicotinic (nAChR) receptors.
- Pentameric
- 16 nicotinic subunits in humans (9α, 4β, γ, δ, ε)
- Many receptor subtypes (subunit combinations)
- Built in ion channel
- 2+ ACh sites
- Responses µs-ms
- Found in CNS and periphery
- important at the skeletal muscle neuromuscular junction and in autonomic ganglia
What are the Nicotinic (nAChR) receptor agonists and antagonists?
- Agonists: nicotine, suxamethonium
- Antagonists: atracurium, tubocurarine, a BTX
Describe the structure of Muscarinic (mAChR) receptors.
- Monomeric
- M1-5 subtypes
- 5 receptor types
- Binding site for G protein (GPCRs)
- 1 ACh site
- Responses ms-s
- Found in CNS and periphery
- Slower than nicotinic receptors
- Main mediators of transmission to effector organs in the parasympathetic branch of ANS
- play a role in a small number of sympathetic synapses too
What are the Muscarinic (mAChR) receptor agonists and antagonists?
- Agonists: muscarine, pilocarpine
- Antagonists: atropine, hyoscine
Describe the structure of Skeletal muscle nAChR.
- 2 ACh binding sites
- All channels are cation channels and are permeable to Na+ & K+ with varying Ca2+ permeability
- Neuronal receptors tend to be more Ca2+ permeable than muscle receptors
- Has 5 subunits: 2x α1, β1, δ, ε/γ (in fetus)
Describe the structure of 2 Brain nAChR.
Bothe widely distributed.
- 2x α4, 3x β2 - (Mostly on presynaptic nerve terminals and neuronal axons - neuromodulation) homo
- 5x α7 - homopentamer with 5 ACh binding sites
Describe the structure of Autonomic ganglia nAChR.
α3 & β4
In the parasympathetic as sympathetic nervous system there is a 2 neuron chain leading from spinal chord (releasing acetylcholine) to effector tissue (nicotinic receptors with α-3 & β-4 subunits). These synapse in the autonomic ganglia.
Describe the structure of Inner-ear hair cells nAChR.
α9 & α10
Name the 2 key structural features of the Acetylcholine (ACh)
- Ester linkage
- where the enzyme acetylcholinesterase cleaves ACh to terminate transmission. Helps the breakdown of ACh - The permanent positively charged nitrogen allows binding to ACh receptors.
- a structural feature that is necessary for it to bind to its receptors.
- Its permanent positive charge means it will not dissolve in membranes
Describe the structure of nAChR
- pentamer of four different types of subunit.
- ACh binding sites are at interfaces of the α subunits with their neighbouring δ and γ/ε
- 2 ACh molecules bind = channel opens and sodium enters the cell = muscle depolarizes, = action potential
- Second transmembrane domain (TM2 red) contains polar residues. Five TM2 domains form the channel lining
- All subunits have the same general structure: 4 transmembrane domains and a large N terminal domain
Describe the structure and function of Acetylcholinesterase.
- Catalyses the breakdown of ACh to choline and acetate.
- Present in the synaptic cleft.
- Catalytic subunits (AChEt)
- Collagen-like tail (ColQ) subunits anchor acetylcholinesterase to the basal lamina
Describe the vesicular release of ACh
- Synaptobrevin, SNAP-25 and syntaxin are collectively known as SNARE proteins (SNAP Receptor).
- When intracellular calcium concentrations rise, the SNARE proteins bind to each other, drawing the vesicle close to the membrane
- The vesicle fuses with the membrane and the contents (ACh) are released into the synapse
