1
Q
what is the CNS?
A
- Spinal cord and brain
2
Q
What is an afferent pathway?
A
taking an affect – from target organ to NS
3
Q
what is an efferent pathway?
A
– making an effect – from NS to target organ
4
Q
What does the ANS efferent pathway include?
A
at least 2 principal neurons that connect spinal cord to target organ
- Efferent neurone which has pre-ganglionic neurone and soma located in the lateral horn of the spinal cord – pre-ganglion neurons – myelinated axons
- This connect to another neurons which has soma in the autonomic ganglia which are parallel to the spinal cord column – post ganglionic efferents are non-myelinated
- Does not necessarily end with a synapse but could be with a varicosity (postganglionic varicosity) which can release NT as it passes along e.g smooth muscle cell in the somatic efferent pathway
5
Q
what is a varicosity?
A
a swollen, bead-like enlargement located at intervals along the branches of postganglionic axons. They function as the site of neurotransmitter storage and release, acting as the synapse between the nerve fiber and the effector tissue (such as smooth muscle, cardiac muscle, or glands)
- varicose veins are swollen veins
6
Q
What does the somatic NS efferent pathway include?
A
- One principle neurone which connects spinal cord to effector organ e.g skeletal muscle NO PRE OR POST GANGLIONIC NEURON
- soma in ventral horn
- Myelinated axon
- Axon ends with synapse which releases NT to trigger contraction in skeletal muscle
- neuromuscular junction
7
Q
are post-ganglionic neurons myelinated?
A
No they are unmyelinated
- post-ganglionic neurons are only in PNS
8
Q
What is the main role of ANS?
A
homeostasis – sweat, shiver etc and also balance and posture
9
Q
What is the stimulus location in somatic system vs autonomic system?
A
somatic = exteroreceptor and (and proprioreceptors) in tendon or skeletal muscle
autonomic = enteroreceptors (and proprioreceptors) - receptor located in viscera or smooth muscle cells
both have proprioreceptors!
10
Q
what are exteroreceptors?
A
near or on the body surface detecting env cues
11
Q
what are enteroreceptors?
A
receptor located in viscera or smooth muscle cells
12
Q
what are interoreceptors?
A
located deep in body monitoring changes and maintain homeostasis
13
Q
where is the PNS located?
A
- Brainstem, SC and sacral part (most cordal part of SC)
- Nerves branching – vagal nerve controls diff branches and organs from lungs to viscera
- Principal neurons in Brain stem and sacral (caudal) and cervical (cranial) parts of SC
- 2 separate branches, not all connected – nerves branch like the vagal nerve which then controls diff organs from lungs to viscera
14
Q
where is the SNS located?
A
- Neurons connected
- Thoracic and lumbar parts of SC only
- Uses fusion ganglia projections to get to other parts of SC - higher up and lower etc
- Principal efferent neurons in Thoracic and lumbar parts of SC (central parts of SC)
- But needs to get to cranial and caudal organs too (at top and bottom of body) so uses fusion ganglia projections which are parallel to the spinal cord where neurons are located below the organs can still reach them
- Chest and lumbar area
- All SNS neurons are connected in SC
15
Q
what is the reflex arc?
A
- Similar to Somatic NS
- Stimulis from periphery – afferent pathway
- Synapses on dorsal root ganglion and dorsal root
- Synapse with pre-ganglionic neuron which sends info by pre-ganglionic neurone to autonomic nervous ganglion where it synapses on secondary ganglion (post-ganglionic) which targets organ
- sensory, relay, motor
16
Q
what is the major difference between ANS and Somatic NS?
A
So major diff is ANS and SNS is that ANS has 2 neurones - pre and post
somatic only has one neutron
17
Q
What ‘readiness’ activities happen in SNS?
A
pupils dilate
HR increases, arterial pressure increases bc of vasoconstriction
airways dilate
blood vessels dilate
GIT activity decreased - - blood flow to skeletal muscles but restrict to stomach
muscle strength increases
- Blood glucose increase, glucose broken down
- Glycolysis
- Cellular metabolism – tailored towards ready to dealing with internal and external stresses
- Increases Mental activity
- Rate of blood coagulation just in case get injured
sweat glands stimulated
urinary system relaxed
penis ejaculation
vagina contraction
18
Q
what ‘relaxation’ activities happen in SNS?
A
pupil constricts
HR decreases
airways constrict
blood vessels constrict
GIT increased
urinary system output increased
penis erection
vagina secretion
19
Q
what does activation of SNS stimulate in the brain?
A
stimulates adrenal medulla to secrete epinephrine and norepinephrine
- Neurons which projects into spinal cord to stimulate catecholamine release but not part of ANS
- Direct effect – nerve to tissue
- But also Humoral effect also by stimulating neurons to release adrenaline and noradrenaline
20
Q
How long does it take to clear catecholamines from blood after the stimulation of the adrenal medullae?
A
- Secreted catecholamines take 3-4 minutes to be cleared from blood
- Increases adrenal secretion - 80% of adrenal secretion is epinephrine (adrenaline)
- Secreted epinephrine can double the level of cellular and tissue metabolism
- Bc if adrenal medulla is stimulated then it can double basal tissue metabolism
- Effect on vasoconstriction and bronchi
- Catecholamines secreted from adrenal medullae act 10 times longer than synaptic catecholamines
21
Q
what’s the difference between catecholamines secreted from adrenal medulla and synaptic catecholamines?
A
- Catecholamines secreted from adrenal medullae act 10 times longer than synaptic catecholamines
22
Q
How are pre-ganglionic neurons arranged in SC?
A
- They synapse secondary neurons which are the post-ganglionic neurons which are located in Para-vertebral ganglia – called parallel bc its parallel to vertebral spinal column
- In some cases, Pre-vertebral ganglia – located close to target organs e.g gut or heart – doesn’t mean there are three neurons but sometimes preganglionic neurone in the SC will bypass paravertebral ganglia and connect directly to pre-vertebral ganglia – mostly for visceral organs
- Most neurons go through paravertebral ganglia
- Preganglionic connects to para which connects to pre-vertebral
freya’s explanation:
PNS has pre and post ganglionic neurons which are between SC and first ganglia and post are after and go direct to target organ
Paravertebral ganglia (form a chain) are ganglia (collection of cell bodies) next to vertebrate
- Preganglionic neurons can synapse in para-vertebral ganglia or pre vertebral ganglia depending on target organ
- If they synapse in pre-vertebral ganglia, they will go through the para-vertebral ganglia but won’t synapse in it
- para-vertebral ganglia and pre vertebral always both start with pre-ganglionic neuron
- Coeliac one goes to liver but for eye it doesn’t have preganglion one goes to para-vertebral ganglionic
23
Q
How are post -ganglionic neurons arranged in SC?
A
- Either synapse in paravertebral ganglia or pre-vertebral ganglia and will then target the organs
24
Q
what is viscera?
A
large, soft organs withins the bodys main cavities like chest, and abdomen – digestive, respiratory, urinary and reproduction systems
25
what is the sympathetic fusion para-vertebral ganglia?
- Pre-ganglionic neurons are not in the cervical segment of the SC but still needs to reach organs that are higher up (more cranial)
- So then have neurons which have their soma located in the thoracic part of the spinal cord to connect through fusion ganglia which reach all the way up to neck which connect to post ganglionic neurons (efferents) like in our arms to target either iris in the eye or heart or bronchi
- Multiple ganglion in the fusion ganglion chain
26
What are the efferents from multiple spinal segments that the Fusion para-vertebral ganglia contain?
- Superior cervical ganglion (C1-C4) – most rostral – targets eye and heart
- Medial cervical ganglion (C5-C6) targets heart and lungs
- and stellate (lowest part – most caudal of lungs) ganglion (C7-T1), most caudal part of the fusion ganglion chain innervate lungs and the heart
- so these are post-ganglionic neurons
27
is the control in the ANS Ipsilateral control or contralateral?
- Most cases, except for some organs in the viscera, the control in the ANS is Ipsilateral control (neurons on same side of body will control organs on that same side of the body, contralateral is opposite side) of organs (exception: intestine and pelvic viscera)
28
how are sympathetic pre-vertebral ganglion arranged?
- Located close to target organ
- Named after associated artery e.g renal ganglia – anterior part of kidneys
- Neurons from SC will synapse to post-ganglionic neurons in pre-vertebral ganglia and spread to target organs which are closely located
- Each pre-ganglionic sympathetic neurons branches can synapse as many as 200 postganglionic neurons – large branching
- Enables divergence of widespread effects
29
what are para-vertebral ganglia?
- Paired clusters of nerves cell bodies running alongside the vertebral column, forming a key part of the sympathetic NS
- Act as relay stations where preganglionic neurons from the spinal cord synapse with postganglionic neurons, sending signals to control involuntary functions in the body wall, limbs and many internal organs, extending from skull to coccyx
- Bilateral – both sides of vertebral colum, lateral (away from the midline) and ventral to the spinal cord
30
what do postganglionic neurons release in ANS?
ACh
31
3 diff ways how pre-ganglionic neurons (which have soma are in the lateral horn) connect to post-ganglion neurons ?
32
where is the soma for pre-ganglionic neurons?
- Soma in the lateral horn
33
which fibres are pre-ganglionic neurons?
- Myelinated B fibres (not as fast as alpha fibres) – have a transmission speed of around 10m/s and enter periphery (exit) through ventral root (front of body)
- White communicating rami (branches, connect spinal nerves to the sympathetic trunk)
34
what are white rami?
White ramus = short, myelinated nerve bundle connecting at spinal nerve (T1-L2) where SNS is in SC, appear white due to high myeline content
35
what are grey rami?
Grey ramus = nerve branch connecting the sympathetic trunk to a spinal nerve, carrying unmyelinated postganglionic fibres from sympathetic ganglia back to spinal nerve to innervate targets like blood vessels, sweat glands and muscles, existing at ALL SPINAL LEVELS unlike white rami which are only T1-l2
- Unmyelinated postganglionic sympathetic nerve fibres so look grey
36
3 diff ways how pre-ganglionic neurons (which have soma are in the lateral horn) connect to post-ganglion neurons
1. In the same ganglion they entered
- Passes through white ramus which is the connecting tract between spinal nerve and column of the ganglia
- Will then connect to post-ganglionic neuron and through the grey ramus will continue to the spinal nerve and reach target organ
- On same rostral/cordal axis – same level
2. Passing up or down to a different ganglion
- Send axons all the way through white ramus either up into fusion ganglion (near neck as no SNS in cervical region of SC) where they connect to post ganglionic neuron
- Or go through white ramus and go below to fusion ganglion where they connect to post ganglionic neuron
- Up or below fusion ganglion to connect to postganglionic neurons
- Not on same level, not on same rostral/caudal axis as pre-ganglionic neurone
3. Exiting via sympathetic nerve to synapse in a peripheral ganglion
- Pre-ganglionic neuron doesn’t connect in para-vertebral ganglia but sends its axon all the way to peripheral ganglion or the pre-vertebral ganglion which is located close to target organ e.g kidney or liver
- Always secondary postganglion neuron that targets effector
- When innervation of viscera or stomach usually
37
what are the fibres in the post-ganglionic sympathetic efferents?
- Unmyelinated C fibres – slow below 1m/s but bc located close to target organ doesn’t really affect propagation
- Gray communicating rami
38
what are the sympathetic afferents?
- Coming from organ back to nervous system
- Sensory ending travels back through white ramus in paravertebral ganglion but uses DORSAL root (back of spinal cord segment) not ventral root like efferents
- Travel through white ramis to SC, through dorsal root and connects to SC segment
39
what are the two separate parts of the PNS?
cranial and sacral
40
what is the cranial parasympathicus?
- Pre-ganglionic neurons in the supraspinal nuclei in medulla or PONs in brainstem, target eye, and lacrimal and salivary glands – produce tears and saliva
- Their efferents form cranial nerves (CN)
- Vagal nerve (X cranial nerve) targets heart, bronchi and viscera
- Consists of CN III, VII, IX, X – other nerves don’t have ANS functions, may have somatic instead – there are 12 cranial nerves but only these four have parasympathetic functions – 3rd, 7th, 9th and 10th
- Visceral control by vagus (CN X)
41
how many cranial nerves are there? how many are PNS?
there are 12 cranial nerves but only these four have parasympathetic functions – 3rd, 7th, 9th and 10th
42
what is the Sacral parasympathicus?
- Located at very caudal end of spinal cord
- Pre-ganglionic soma in SC, target and innervate viscera, bladder, anus and genitalia
43
what are the four PNS cranial nerves and what are their nuclei (in the medulla)?
- 3rd cranial nerve Oculomotor nerve is (III) – Edinger-westphal nucleus
- 7th cranial nerve is Facial nerve is (VII) – superior salivatory nucleus
- 9th is Glossopharyngeal nerve (IX) – inferior salivatory nucleus
- 10th is Vagus nerve (X) – dorsal motor nucleus of vagus - Nucleus ambiguous also CN S and part of CN IX
- Some of these PNS nerves also have somatic NS functions – branches that relate to sensory or motor functions but only these four have PNS functions, others don’t
44
what do the cranial PNS nerves target?
- 3rd is oculomotor – Edinger-westphal nuclei – targets pupil, important for dilation of pupil and ciliary muscles
- 7th is facial – two branches of the facial nerve which both have preganglionic neurons in superior salivatory nuclei – to target lacrimal glands in the eyes to stimulate tears, also stimulate salivary glands to produce saliva
- 9th is pharyngeal – has preganglionic neurons in inferior salivatory nuclei which innervates and stimulates salivary glands but the parotid gland
- 10th is vagus
45
why is the 10th cranial nerve the most important?
the vagal nerve
- V thick and many branches so targets many things esp heart and viscera
- Main preganglionic location is in Dorsal nucleus of the vagus in medulla oblongata
- Also has preganglionic neurons in Nucleus ambiguus also in the medulla
affect HR and motility of gut but also sensory function of what organs are doing
46
what modulates the ANS?
The CNS!
- - The hypothalamus (a part of the diencephalon) controls many basal body functions and can modulate ANS
- Neurons located in hypothalamic nuclei will affects strength of output of SNS and PNS
47
what happens if you have an injury above the medulla?
- If have damage or injury above the medulla (where have PNS preganglionic neurons) then only lose output of neurons in medulla but wont lose control of the actual PNS neurons over downstream functions
- So Basal control of arterial pressure is still in tact
48
What happens if you have an injury below the medulla?
- If injury below medulla, it cuts off axons from nuclei in medulla to target the organs so no control of blood pressure from PNS, whereas control of blood pressure from SNS is still in tact bc neurons in sympathetic NS are much lower
- Arterial pressure falls to less than one-half normal
- SC injury below medulla will kill off any descending axons from PNS while leaving PNS in tact as medulla is fine
49
What is the enteric nervous system of the GI tract?
- Have longitudinal nerves – in longitudinal muscles which allow peristalsis
- Or circular muscle
- Each have their own plexi (nerves in the gut that control the gut) - myenteric and meissners
50
what is the myenteric plexus?
Myenteric nerve plexus: motility
- Just under longitudinal nerves
- Important for peristalsis – movement of gut
51
what is Meissners plexus?
Submucosal (Meissner’s) nerve plexus: fluid/ion regulation
- Closer to epithelial of gut
- Regulates transports of ions and fluids into gut
52
what is the enteric NS regulated by?
This part of NS is regulated by ANS by PNS and SNS, it can also act on its own!!! Without external input
53
what are the intestinal glands controlled by?
- The intestinal glands are controlled by the intestinal enteric NS and much less by the ANS
- PNS stimulates enteric NS: higher motility and secretion
SNS doesn’t normally affect function of enteric NS except in stress
54
what happens to enteric NS in stress?
SNS doesn’t normally affect function of enteric NS except in stress
- Limits blood to gut to stop peristalsis
- but very strong SNS stimulation inhibits it: increased tone of the sphincters, decreased motility and secretion
55
What is the dominant vagal innervation of the enteric NS?
- Tenth cranial nerve innervates whole fundus and body of stomach
56
What do myenteric neurons get stimulated by?
by Ach or PNS – it depolarizes neurons to increase potential until voltage gated sodium channels activated and neurons fire
- If stimulation too large, then doesn’t allow recovery of APs and repolarization cant occur and limits firing frequency
- SNS – if lots of noradrenaline – hyperpolarises neurons and cant fire APs either
57
What happens in intrinsic peristalsis?
- Some segments of the gut need to be contracted and some need to be relaxed to allow bolus of food in cordal direction
- Neurons in area of contraction will help stimulate smooth muscles cells of gut and also inhibit other segments of the gut so they relax
- This is done by ACh or ATP
58
what is intrinsic peristalsis stimulated by?
- By Ach and ATP
59
What are the role of glia in the enteric NS?
Lots of glia in enteric NS
- Glia are not excitable cells, cant fire APs
- But Regulate NT recycling
60
what did single-cell RNA sequencing reveal about the enteric NS?
- Analysis of profiling which neurons and glia in enteric NS
- Used a single nucleus RNA seq and found 5 subtypes of neurons in NS which differ by transcriptional signals
- And then found 3 different glial subtypes
61
how long are pre-ganglionic fibres in SNS vs PNS?
in parasympathetic - long
in sympathetic - short
62
What is the neurotransmitter of pre ganglionic neurons in SNS and PNS?
both ACh
63
what are the receptors that preganglionic neurones synapse with in PNS and SNS?
nicotinic cholinergic receptors - N2ACh4
- specifically nicotinic type 2
64
What are post-ganglionic neurones like in PNS and SNS?
parasympathetic is short
sympathetic is long
65
which neurotransmitters are released from post-ganglionic neurons in PNS and SNS?
ACh in parasympathetic
Noradrenaline or adrenaline from sympathetic
66
which receptors do post-ganglionic neurones synapse with in SNS and PNS?
Muscarinic cholinergic receptors in parasympathetic
Alpha or beta adrenergic receptors in sympathetic
67
what are cholinergic neurons?
nerve cells that use ACh to transmit signals
68
what is the difference in affinity in Alpha and beta adrenergic receptors?
Alpha adrenergic receptors have higher affinity for noradrenaline whereas beta receptors have higher affinity for adrenaline
69
Are all sympathetic post-ganglionic neurons adrenergic?
Most are but not all sympathetic postganglionc neurons are adrenergic, there are some exceptions
- Sweat glands – use cholinergic neurons post-ganglion (muscarinic receptor)
- Arrector pili muscles
- and some blood veseels
70
what do chromaffin cells in the adrenal medulla release?
release adrenaline and noradrenaline as hormones into blood stream, not at synapses
71
what are the two types of receptors?
Ionotrophic and metabotropic
72
What are ionotrophic receptors?
- ion channels that act as receptors and channels – ACh binds and changes the conformation so can then have efflux or influx of ions
- has 5 subunits
- nACHR opens with Ach binding to extracellular part
- v fast opening – nanometers scale
- response is brief and fast
- influx or efflux of ions when triggered by a neurotransmitter
- changes depolarization of the cells
73
what are metabotrophic receptors?
- GPCRs usually
- Not directly opened by neurotransmitters but usually in vicinity or attached to a receptor for a neurotransmitter
- NT binds, changes conformation, alpha subunit dissociates, uses secondary protein or directly bind to ion channel which then changes conformation and allow movement of ions and depolarize or hyperpolarize the cell and trigger or dampen an AP signal
- response is slower but longer-term
- E.g mACHr – muscarinic
- can also hyperpolarize fibres and make them harder to fire or excite neurons
74
what are the three classes of GPCRs?
Gas – stimulating adenylyl cyclase so increases cAMP
GalphaI – inhibits Adenylyl cyclase so doesn’t produce cAMP – also needs GTP to work
Galphaq – connected to PLC – cleaves PIP2 to IP3 which acts as the secondary messenger – then Ca2+ and IP1?
75
Where are muscarinic ACh receptors found?
cardiac, smooth muscle or exocrine glands
76
Where are nicotinic ACh receptors found?
ganglia, adrenal gland, neuromuscular junction
77
why are muscarinic receptors named that?
activated by muscarine - amanita muscaria – means fly – from mushroom, in old times put sugar on it, toxin draw in, fly draw to it and dies bc muscarinic receptor overactivated
78
why are nicotinic receptors named that?
activated by nicotine - alkaloid activates it in nicotiana tabacum – mimics natural Ach NT – triggers contraction of smooth muscle in target organ
79
what activates both MAChRs and NAChRs?
- ACH activates both receptors
Eventually broken down by AChE – breaks down ACH into choline and acetic acid which can be recycled by acetyl CoA and CAT
80
What does ACh get broken down into?
Acetic acid and choline
81
what is choline recycled by once broken down by AChE?
acetyl CoA and CAT
82
How was the first neurotransmitter found and what was it?
ACh
- Lowei postulated vagal nerves stuff that there was something that activated both receptors
- Isolated two frog hearts
- One had a vagal nerve still attached one was innervated, no nerves
- Connected both by a tube both
- When vagal nerve stimulated by electrodes, something was released that travelled to the other heart
- Now know that Parasympathetic lowers contraction of heart which was what happened – lower frequency and amplitude and then a delay but also the same in the other heart
- So know what was released from vagal nerve dampened heart beat
83
Does nicotine act on PNS or SNS?
Both
- Nicotinic receptors on pre and post synaptic neurons in para and sympathetic
- In Sympathetic has stronger effect on bronchi and blood vessels, para has smaller affect
- So ingesting nicotine mostly affects sympatheticus more - effects blood vessels
- If abuse nicotine for a long time, affects HR – arrythmia and hypertension as it affects blood vessels
84
Why is Acetylcholinesterase important?
- Determines frequency and strength of AP signal in synaptic cleft
85
What is myasthenia gravis?
a neurodegenerative disease that causes lower amount of ACH and neurodegeneration of noradrenergic neurons and choline
- immune system produce antibodies that block or destroy cholinergic receptors
- causes muscle weakness especially eyes - drooping
86
how do you treat myasthenia gravis?
- Reversible ACh inhibitors e.g Pyridostigmine
- immunosuppressants
- monoclonal antibodies
can also be used for glaucoma
87
what is glaucoma?
Glaucoma is a group of eye conditions that damage the optic nerve—essential for vision—often due to high fluid pressure inside the eye. It is a leading cause of irreversible blindness, typically progressing slowly without early symptoms. While vision loss cannot be reversed, early detection through routine eye tests and treatment can prevent further damage.
88
what are irreversible AChE inhibitors?
used as chemical weapons– toxic – sarin, VX and Novichok
- Potent and act in sub nanomolar conc, die from poisoning straight away as blocks AChE so cholinergic neurons will leave Ach to act on cholinergic receptors – overacting them and the systems
89
what do irreversible AChE inhibitors cause?
- Overactive cranial PSNS – acts on glands to Increase salivation and production of tears
- Overactive SNS – acts on glands to increased sweating, elevated HR and BP, leads to death bc of arrythmia
90
so can ionotropic receptors be nicotinic or metabotropic?
Yes Ionotropic – nicotinic or metabotrophic – are cholinergic ones
- Bind both Ach
91
how many subunits are in nAChRs?
5 - Pentameric bc they're ionotropic
- Can be hetero-pentamaric nACHR (different subunits) or homo-pentarmeric nACHR (same subunits)
92
where are heteropentameric nAChRs found?
- Heteropentarmeric is muscle cells
- can also be neurones in CNS
93
where are homopentameric nAChRs found?
- Homo is normally neuronal
94
which subunit in ionotropic nAChRs has the highest homology?
The alpha subunit
95
Are cholinergic receptors only expressed in ANS?
No, nAChR are in brain too – pyramidal neurons in hippocampus are cholinergic
96
where are the genes for the nAChRs?
- All over genome, not clustered
- Quite large proteins
97
What is the molecular structure of the alpha and beta subunits of nAChRs?
specifically alpha3 and beta4 subunits
- has hinges region where ACh binds and changes the conformation of the extracellular part of the receptor
- this is translated and connected to ion selective pores and the amino acids residue in the chain and make the Na+ fit so it can flow through
98
how do you record nAChRs?
Patch clamp physiology
- Control how much voltage flows through cell
- Can record current
- Nictotine induces ionic current carried by nAChRs
- can induce them with different concs of ACh and see recording
- can also do single channels - (single patch clamp) to record current in a single receptor
- Deflections in the recording is where channel opens
- If hyperpolarize membrane, get a greater driving force for K+, if you depolarize it, it is less
99
What family are mAChRs?
– metabotrophic
- Part of GPRCs and in rhodopsin-like family
- Amine receptors bc theyre cholinergic
100
how many known types are there for mAChRs?
- 5 known types M1 (Gq), M2 (Gi), M3 (Gq), M4 (Gi), M5 Gq
- they either decrease cAMP or use PLC
101
what do mAChRs do that are Gi?
- Gi decrease cAMP and so there is a decreased Ca2+ influx and increased efflux of K+ which hyperpolarizes the cell and makes it harder to excit
- In M2 this decreases heart rate and force
- Gi decrease cAMP and so there is a decreased Ca2+ influx and increased efflux of K+ which hyperpolarizes the cell and makes it harder to excit
- In M2 this decreases heart rate and force
102
what are nAChRs blocked by?
Curare - used by tribes for hunting
- so blocks ion channels
- Response is brief and fast
- Located at NMJ, autonomic ganglia and to a small extent the CNS
103
What are mAChRs blocked by?
- Blocked by atropine – from deadly nightshade – used to apply to eyes to inhibit AChR which dilated pupils – mimic sexual arousal but could also kill theirself
- Linked to 2nd messenger systems through G proteins
- Response is slow and prolonged
- Found on myocardia muscle, certain smooth muscle and in discrete CNS regions
104
does curare kill by acting on ANS or PNS?
blocks nAChRs
- Kills by acting on neuromuscular system
- Kills by blocking somatic synapses in the skeletal muscle, neuromuscular system, blocking breathing
- So blocks nicotinic receptors in SNS and PNS but also ACh receptors in somatic nervous system that connects to skeletal muscle so kills breathing muscles before it can dysregulate the PNS
105
how does muscarine work?
on mAChRs
- Decreases HR
- And increases motility and secretion in the GI tract
- Acts through PNS
- Muscarinic metabotrophic are between postganglionic neurons and target organ
106
Which type of nAChRs are used in pre-ganglion in the somatic nervous system and which are used in ANS?
Somatic NS - N1 - Ach between SC and neuron and axon and skeletal muscle and then uses adrenergic receptors on post
ANS - N2 - ACh all the way through but then uses muscarinic in post
107
Which nAChR receptors are used for pre-ganglions in the SNS?
from adrenal medulla – uses Ach and then N2 receptor using adrenaline so adrenergic receptors
- And from sweat glands – so these last two are actually PNS
108
What are the adrenergic receptor subtypes?
a1 - blood vessels mainly
a2 - presynaptic terminals mainly
b1 - heart
b2 - bronchi mainly but also visceral smooth muscle
b3 - adipose
so they noradrenaline or adrenaline bind to alpha or beta subunits
- Tissue-specific distribution, predominantly
- Alpha and beta adrenergic receptors are expressed in different organs but still NT is the same
109
what do A1 adrenergic receptors do?
vasoconstriction of smooth muscles and increase BP, in gastrointestinal tract, it causes relaxation and also salivation in salivary glands
110
what do A2 adrenergic receptors do?
they increase contraction or inhibit insulin release - function depends on which cells are expressed in - smooth muscle contracts
also platelet aggregation
111
what do B1 adrenergic receptors do?
they cause smooth muscle to relax but they also increase heart rate and increase force of cardiac muscle contraction
112
what do B2 adrenergic receptors do?
increase bronchodilation, vasodilation but in visceral smooth muscle they cause relaxation
113
what do B3 adrenergic receptors do?
lipolysis in adipose tissue
114
what family are adrenergic receptors?
also - Metabotrophic in pm
- GPCRs
- Amine receptors
- and have alpha or beta subunits with A1, A2 and beta subtypes
115
how many known adrenergic receptors are there?
- 9 diff known types of adrenergic receptor
116
what do Alpha1 adrenergic receptors do?
they are Gq so connected to PLC
117
what do Alpha2 adrenergic receptors do?
A2 = Gi
- decrease cAMP
118
what do Beta adrenergic receptors do?
Beta = Gs
- increase cAMP by adenylyl cyclase
although B2 and B3 can have Gs or Gi effects depending on which cells expressed in
- May have opposite affect depending on where it is
119
what effect do alpha adrenergic receptors have?
- vasoconstriction of smooth muscle – increase BP
- Opposite to PNS
120
what effect do beta adrenergic receptors have?
- Increase contractility and strength of contraction in heart and strength of contraction
- Beta blockers – meds for curing basal types of hypertensions
121
where do noradrenaline and adrenaline derive from?
adrenaline derived from tyrosine aa
122
how are noradrenaline and adrenaline converted from tyrosine?
- DOPA decarboxylation to produce Dopamine which can also act as a NT
- Converted by dopamine B-hydrolase to noradrenaline
- Then changed by phenylehtanolamine and methyltransferase
- These add a methyl group and so it forms adrenaline
- Actually goes through 3 aas
123
what are Adrenergic Alpha1 agonists used for?
nasal decongestant
- Bc constrict blood vessels in nasal epithelia so then produce less mucus
124
what are Adrenergic Alpha2 antagonists used for?
– antagonists to treat impotence – help to vasodilate genitalia
125
what are Adrenergic Beta1 agonists used for?for?
antagonist as antihypertension – beta blockers as reduced heart contractility
- so Millie
126
what are Adrenergic Beta2 agonists used for?for?
agonist bronchodilators in asthma
SNS – flight or flight so expand lung capacity – so B2 agonists does this basically same as adrenaline
127
what are the drug types that act on the ANS?
nicotinic agonists
sympathomimetics
sympatholytics
parasympatholytic
anticholinergics
128
what do nicotinic agents do?
mimic ACh in prę-ganglion and release noradrenaline in SNS and PNS
- cause hypertension
e.g nicotine
129
what do sympathomimetics do?
mimic noradrenaline in post-ganglion in SNS but no effect on PNS
- cause increased sympathetic tone and release or increase diameter of pupil = mydriasis
- used as decongestants too
e.g LSL or phenylephrine
130
what are Sympatholytics?
blocks adrenergic receptors
- limit activity of SNS but no effect on PNS so then as PNS isn't changed, there's increased parasympathetic tone causing hypOtension
– e.g beta-blockers like propranolol treats hypertension, PNS prevails so then vasodilation through nitric oxide release from PNS neurons
131
what do Parasympatholytics do?
no effect on SNS (except sweat gland) but blocks mAChRs post ganglion in PNS
– increase SNS tone as blocks PNS
e.g drugs like atropin and oxybutynin which is a bladder relaxant – relaxes smooth muscle in bladder, atropine blocks AChR on postsynaptic neurons side
132
what do Anticholinergics drugs do? –
no effect on SNS but blocks mAChR on PNS so overall increased sympathetic tone
e.g atropine like in parasympatholytics
133
Physiology
flashcards
Decks in class (14)
# Cards
-
Core concepts and membrane modelling and ionic balance58
-
Cell physiology75
-
Endocrinology9
-
GI TRACT AND LIVER270
-
Respiratory physiology142
-
ANS133
-
Neuromuscular system117
-
control and regulation of blood pressure109
-
Control of fluid volume111
-
Control of pH61
-
CW243
-
Reproduction and fertility98
-
The challenge of exercise112
