ANS & NMJ Flashcards
What NTs are used in the ANS
ACh and noradrenaline
ACh => cholinergic neurotransmission
NA => noradrenergic neurotransmission
What NT is used at the neuromuscular junction
ACh
=> cholinergic neurotransmission
What does cholinergic neurotransmission at the NMJ permit
Voluntary skeletal muscle contraction
Breakdown of nervous system
In the ANS, name the NTs used
PS & S neurons use cholinergic and noradrenergic NT to produce their effects
Function of the ANS
Conveys all the outputs from the CNS to the rest of the body (except for the somatic motor innervation of the skeletal muscle)
Name the main processes regulated by the ANS
Heartbeat
Contraction and relaxation of SM
Hormonal (endocrine) and glandular (exocrine) secretions
Energy metabolism
Where are the ganglia located in the sympathetic nervous system
Alongside the vertebrae - PARAVERTEBRAL SYMPATHETIC CHAIN
Where are the ganglia located in the PS nervous system
Ganglia are located adjacent to or within the target
Longer pre-ganglionic fibres
What structures in the body only have a sympathetic innervation
BVs
Adrenal medulla
Sweat glands
Kidney
Liver
Spleen
Sympathetic NS
Fight or flight
Prepares body for activity
Operates under normal conditions to maintain homeostatic tone
PNS
Rest and digest
Acts to conserve energy
Operates under normal condition to maintain homeostatic tone
Overview of physiology of ANS
Within the sympathetic nervous system, differentiate between the NTs released in preganglionic vs postganglionic neurons
What is the exception to this rule
Preganglionic - cholinergic (ACh)
Postganglionic - noradrenergic (NA)
EXCEPT for sympathetic innervation of sweat glands - the postganglionic neuron uses ACh
Differentiate between adrenaline and NA
NA is a precursor of adrenaline
Noradrenaline is a NT that is delivered from the nerve terminal
Adrenaline is delivered by blood
Receptors of ACh in SNS
nicotinic receptors
Receptors of NA in SNS
alpha or beta adrenoceptors
Differentiate between preganglionic and postganglionic neurons in the PSNS
Preganglionic => cholinergic
Postganglionic => cholinergic
What receptors does ACh act via at:
- PS ganglia
- PS targets
- Nicotinic receptors
- Muscarinic receptors
Summary of ANS and NMJ
Main ways to enhance NT
Use agonists to mimic NT
Inhibit enzymes that metabolise NT
Inhibit transporters responsible for taking NT out of synapse
Main ways to reduce NT
Use antagonists to block NT
Inhibit enzymes that synthesise NT
Name the 2 types of ACh receptors
Nicotinic - nicotinic actions of ACh can be mimicked by nicotine
Muscarinic - muscarinic actions of ACh can be mimicked by muscarine (an extract from a poisonous mushroom)
Where is ACh more potent
At muscarinic receptors
i.e. larger doses are required to activate nicotinic receptors
Name the 3 subtypes of nicotinic receptors
Muscle - skeletal
Ganglion (ANS)
CNS (brain)
Name the 5 subtypes of muscarinic receptors and where each is found
M1 - acid - gastric parietal cells
M2 - heart - slows HR
M3 - glandular/SM (contraction)
M4
M5
What TYPE of receptors are all nicotinic ACh receptors
Ligand-gated ion channel receptors
Therefore they mediate fast excitatory effects
Describe the permeability of nicotinic ACh receptors
They are permeable to Na+ and cause depolarisation of the post-synaptic cell
What does activation of the nicotinic ACh receptor (muscle type) lead to
Excitation of muscle cells
What does activation of the nicotinic ACh receptor (ganglion type) lead to
Excitation of post-ganglionic neuron
Activation of alpha/beta adrenoceptors results in…
HR and force increases
Vascular SM contracts, BP increases
Visceral SM relaxes
Glandular secretions reduce
Activation of muscarinic receptors results in…
HR and force decreases
Visceral SM contracts
Glandular secretions increase
Describe the function of the muscle type of nicotinic receptor
Located at the synpase between the somatic motor neurons and the skeletal muscles (NMJ)
Located at the muscle cells
Mediates fast cholinergic contraction of the skeletal muscles
Function of the ganglion type of nicotinic receptor
Located at the synapse between the preganglionic and postganglionic neurons of the ANS
Located on the post ganglionic neuron
Mediates fast cholinergic NT between the pre and post ganglionic neuron
What type of receptors are all muscarinic ACh receptors
GPCRs
hence mediate slow excitatory or inhibitory effects
What is the function of the CNS type of nicotinic receptor
Located at the synapse between neurons in the brain
Mediates fast cholinergic NT in the brain
What do M1, M3 and M5 all have in common
Gq linked (excitatory e.g. SM, glands)
What do M2 and M4 all have in common
Gi linked (inhibitory e.g. heart)
How do GPCRs function
Affect cell function indirectly by coupling to a G protein
G protein acts a go between linking the receptor and a target protein
G protein interacts with the target protein causes an increase or decrease in the levels of 2nd messenger signal within the cell
Describe signal transduction by the M1, M3 and M5 subtypes
- These receptors are coupled to a G protein - Gq
- Target for Gq = phospholipase C
- Pohspholipase C is activated by interaction with the G protein
- This causes release of the 2nd messengers IP3 and DAG
- Excitatory effects on cell - e.g. slows heart
Describe the signal transduction by the M2 and M4 subtypes
- These receptors are coupled to a G protein - Gi
- Target for Gi = adenylate cyclase
- Adenylate cyclase is inhibited by interaction with G protein
- This reduces the amount of 2nd messenger cAMP in the cell
- THis has inhibitory effects on the cell (e.g. visceral SM contraction and glandular secretion)
Function of the M1 receptor
Located on gastric parietal cells
Mediates slow excitatory effects i.e. stimulation of acid secretion
Function of M2 receptor
Located on heart
Mediates slow inhibitory effects (slows both rate and force of cardiac contraction)
Function of M3 receptor
Located on glands and SM
Mediates slow excitatory effects e.g. stimulation of glandular secretions and contraction of SM
Cholinergic receptor that mediates constriction of pupils
M3
Cholinergic receptor that mediates stimulation of saliva flow
M3
Cholinergic receptor that mediates a decrease in HR
Cholinergic receptor that mediates a constriction of bronchi
M3
Cholinergic receptor that mediates the stimulation of stomach peristalsis and secretion
M3
Cholinergic receptor that mediates an increase in gut motility
M3
Cholinergic receptor that mediates the contraction of the bladder
M3
What are the 2 types of adrenergic receptors
Alpha adrenoceptors - α1 and α2
beta adrenoceptors - β1, β2, β3
What is the distinction between alpha and beta based on
AGONIST POTENCIES
α-adrenoceptors - noradrenaline → adrenaline → isoprenaline
β-adrenoceptors - isoprenaline → adrenaline → noradrenaline
What type of receptors are adrenergic receptors
GPCRs
alpha 1 has what type of link as a GPCR
Gq
alpha 2 has what type of link as a GPCR
Gi
Beta 1, 2 and 3 have what type of link as a GPCR
Gs linked
Signal transduction by the alpha 1 subtype of adrenergic receptor
Like the M1, M3, M5 subtypes of muscarinic ACh receptors, this subtype is linked to Gq
Signal transduction by alpha 2 subtype of adrenergic receptor
Like the M2 and M4 subtypes of muscarinic ACh receptors, this subtype is also linked to Gi
Signal transduction by the beta 1, 2, and 3 subtypes of adrenergic receptor
- Coupled to a G protein - Gs
- Like Gi, the target for Gs = adenylate cyclase
- Adenylate cyclase is activated by interaction with the G protein
- Increase in the amount of the 2nd messenger cAMP in the cell
- This has excitatory OR inhibitory effects on the cell
α1
Location
Physiological effect
- vascular SM and liver
- VasoC and glycogenolysis
α2
Location
Physiological effect
- Vascular SM and glands
- VasoC and decreased glandular secretion
β1
Location
Physiological effect
- Heart
- Increased cardiac rate and force
β2
Location
Physiological effect
- Bronchial SM, visceral SM, skeletal SM, liver
- relaxation/dilation (bronchial SM)
Relaxation of visceral SM
Contraction/tremor of skeletal muscle
glycogenolysis in liver
β3
Location
Physiological effect
- Adipose tissue
- Lypolysis
What does salbutomol treat
Both premature birth and asthma
Adrenergic receptor subtype(s) that mediate these sympathetic effects
Steps in thinking about ANS and NMJ
e.g.
Gastric ulcer
Stomach
Reduce secretion of acid to allow ulcer to heal
The PS system stimulates acid secretion into stomach
This system uses ACh at muscarinic receptors at its targets
ANTAGONISTS will help
Muscarinic antagonists are used to prevent ACh secretion in stomach
