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PCL469 > Lecture 9: Intro to Peripheral Nervous System (ANS) > Flashcards

Lecture 9: Intro to Peripheral Nervous System (ANS) Flashcards

1
Q

Briefly, what input and output is coming to and from the spinal cord from the periphery?

A

input: sensory info and info from the autonomic NS (both PNS and SNS)

output: somatic info and also autonomic info (from both PSNS and SNS)

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2
Q

How does neurotransmission work at the chemical synapse?

A

nerve impulse arrives at the terminal, voltage gated calcium gates open, release of Ach-filled vesicles, binding of Ach to receptor on post-synaptic density, influx of sodium

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3
Q

Most tissues are innervated by both the…

A

PSNS and SNS branches of the ANS, but have opposing effects

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4
Q

The autonomic nervous system regulates

A

homeostasis and emotions

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5
Q

Unique features of the PSNS

A
  • preganglionic neurons are longer and go closer to the effector organs, meaning postganglionic neurons are shorter
  • ACh is used as a NT at both synapses
  • nerves originate at the brainstem and sacral regions
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6
Q

Unique features of the SNS

A
  • preganglionic neurons are shorter and synapse in the sympathetic ganglia chain that runs parallel to the spinal cord
  • the synapse between the postganglionic and the effector organ involves NE instead of Ach
  • neurons originate in the thoracolumbar region of the spinal cord from the lateral horn
  • the SNS is more diffuse - one postganglionic fibre branches and synapses with many more effector organs
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7
Q

Do all preganglionic fibres of the SNS synapse at the sympathetic ganglia?

A

No, a few exceptions:
- the preganglionic fibre to the adrenal medulla is long, doesn’t synapse in the ganglionic chain, and also doesn’t synapse on a postganglionic neuron at all. It synapses right onto the adrenal medulla, releases ACh onto nicotinic Rs, the medulla then releases NE and E into the blood stream
- A central nerve comes off the lateral horn of the thoracolumbar segments and continues through a splanchnic nerve to supply the viscera and synapse in the collateral / prevertebral ganglia (the celiac, superior mesenteric, and inferior mesenteric ganglia)

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8
Q

Adrenal medulla

A

sympathetic preganglionic fibre synapses on the adrenal medulla which then releases a combination of 80% epinephrine and 20% norepinephrine (and a tiny bit of DA)

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9
Q

Neurotransmitters of the ANS

A
  • somatic nervous system is all Acetylcholine (ACh)
  • preganglionic fibres of SNS and PSNS are both ACh
  • postganglionic of PSNS is ACh
  • postganglionic of SNS is NE
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10
Q

How is ACh made, packaged, and broken down?

A

choline is brought into the cell by a choline transporter, within the cell choline acetyltransferase (ChAT) links acetyl coA and choline, ACh is packaged into vesicles which then get released
acetylcholineesterase then breaks down ACh in the synapse

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11
Q

Hemicholine

A

blocks uptake of Choline by the choline transporter in the presynaptic cell (can’t make ACh)

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12
Q

Vesamicol

A

Stops presynaptic vesicles from filling with ACh

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13
Q

metabolic pathway of catecholamine synthesis

A
  • tyrosine -> LDOPA via tyrosine hydroxylase
  • LDOPA -> DA via dopa decarboxylase
  • DA -> NE via DA-beta-hydroxylase
  • NE -> Epi via
    the enzymes that are in the particular vesicle determine whether NE or E is made
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14
Q

What are the implications of transport pumps being ATP-dependent?

A

They can be targeted:
- cocaine targets DAT
- Imipramine and amitriptyline target NET and SERT
- reserpine targets VMAT2 (vesicular packaging)

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15
Q

How are catecholamines broken down?

A

Catecholeamine-o-methyl-transferase (COMT) breaks down catecholeamines in the periphery

MAO (which is usually in the neuron) also breaks down down catecholamines

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16
Q

Classes of Receptors in the ANS

A

Cholinergic receptors
- nicotinic and muscarinic receptors

Adrenergic receptors
- alpha and beta adrenergic receptors

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17
Q

compare and contrast receptors of the ANS

A
  • Alpha adrenergic, beta adrenergic, and muscarinic receptors are all GPCRs while nicotinic receptors are ligand gated ion channels
  • nicotinic and musc receptors bind ACh, while adrenergic receptors bind epi and ne
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18
Q

nicotinic receptors

A

Cholinergic receptor
- ligand-gated ion channel
- opens and lets calcium and sodium cations in
- leads to depolarization

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19
Q

muscarinic receptors

A

Cholinergic Receptor
- GPCR
- effect depends on the target cell and the signalling molecules (could open channels or cause intracell signalling cascade)

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20
Q

alpha adrenergic receptors

A

GPCR
most common of the adrenergic receptors. Kind of expressed everywhere
bind Epi and NE (NE preferentially)

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21
Q

Beta adrenergic receptors

A
  • also GPCR
  • more selectively expressed
  • ALL of these activate AC to increase cAMP
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22
Q

subtypes of nicotinic cholinergic receptors

A

made up of 5 subunits
- either alpha 1-9, beta 1-4, and gamma, delta, or epsilon
- the physiological effect depends on the makeup of the receptor (subunits)
- the most common in the PNS is a makeup of
2 alpha-3 and 3 beta-4

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23
Q

subtypes of muscarinic cholinergic receptors

A

there are m1-m5 subtypes
- m1, m3, and m5 are all excitatory and act through Gq. Phospholipase C activity activates IP3 and DAG which increase intracellular calcium and PKC activity, respectively
- m2 and m4 are inhibitory and act through Gi (reduce cAMP by inhibiting AC)

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24
Q

DMPP

A

agonist of nicotinic receptors in the PNS

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25
Q

hexamethonium

A

antagonist of PNS nicotinic receptors

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26
Q

Ach, muscarine, and carbacol all act on which receptor and do what?

A

muscarinic receptors
- they’re all agonists

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27
Q

atropine and scopoloamine both act on which receptor and do what?

A

muscarinic receptors
- all antagonize

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28
Q

Alpha1 adrenergic receptor signalling cascade

A

Remember from psy396! Alpha1 are excitatory and act through Gq (can draw a q with 1 line)

Gq –> PLC –> increase calcium (depolarization)

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29
Q

selective agonist of the alpha-1 receptor

A

phenylephrine

30
Q

selective antagonist of the alpha-1 receptor

A

prazosin

31
Q

Alpha2 adrenergic receptor signalling cascade

A

remember psy396
- i is written with 2 pen strokes, so alpha 2 is inhibitory
Gi inhibits AC which reduced cAMP

32
Q

Alpha2 adrenergic receptors are located only on the postsynaptic density true or false

A

false, they’re found on both the pre and the post

33
Q

selective agonist of alpha 2 adrenergic receptor

A

clonidine

34
Q

selective antagonist of alpha 2 adrenergic receptor

A

Rauwolscine

35
Q

Beta adrenergic receptor signalling cascade

A

All of the beta subtypes are Gs linked meaning they increase cAMP by activating AC. This increases PKA activity which phosphorylates:
- voltage gated ion channels
- transcription factors (CREB) in DNA
- metabolic enzymes like glycogen synthase

Usually this is excitatory ?

36
Q

How are Beta 1 and beta 2 receptors different

A
  • they both go on to activate PKA but PKA phosphorylates different things (microdomain changes)
  • beta1 binds epi and NE with equal affinities, but beta2 binds epi with much higher affinity
37
Q

Selective beta1 adrenergic agonist

A

dobutamine

38
Q

selective beta1 adrenergic antagonist

A

metoprolol

39
Q

selective beta2 adrenergic agonist

A

terbutaline, salbuterol

40
Q

selective beta2 adrenergic antagonist

A

ICI11855

41
Q

As levels of epi in the blood rise, are beta-1 or beta-2 adrenergic receptor effects lost? why?

A

Beta-2 adr effects are lost
beta2 adrenergic. receptors bind epi with high affinity over NE, so when epi signal is low we see beta2 adr receptor signalling. As these epi levels rise, beta1 adr receptors are more highly activated and you mask the effects of beta2.

42
Q

Relative affinities of the adrenergic receptors for their ligands

A

Alpa1 and alpha2: epi and NE are kinda the same, maybe epi a bit more

Beta1: Epi = NE

Beta2: Epi» NE

Beta3: NE > Epi

43
Q

IPE =

A

isoproterenol, binds alpha and beta adrenergic receptors though with opposite affinities (alpha poorly and beta really well)

44
Q

Why does modulation of the SNS result in more diffuse effects?

A

The actual structure of the SNS is more diffuse. The PSNS is more localized and the ratio of post ganglionic fibres to effector organs is closer to 1:1 or 1:2 (they branch a lot less).

  • SNS postganglionic neurons branch and throw NE onto a whole bunch of effector organs
45
Q

Where are alpha1 adrenergic receptors found?

A

vascular smooth muscle
pupils
genitourinary smooth muscle
liver
GI smooth muscle
heart

46
Q

Where are alpha2 adrenergic receptors found?

A

CNS
platelets
autoreceptors on adrenergic nerve terminals
some vascular smooth muscle
adipose tissue
pancreatic islet cells

47
Q

Where are beta1 adrenergic receptors found?

A

CNS, cardiac muscle, kidney

48
Q

Where are beta2 adrenergic receptors found?

A
  • vascular, bronchial, GI, and GU smooth muscle cells (think. this will give it blood, breathing, digesting effects and effects in the pee and sex systems)
  • Skeletal muscle
  • liver
  • nerve terminals
49
Q

Where are beta3 adrenergic receptors found?

A

adipose, gallbladder, bladder

50
Q

where are M1 muscarinic receptors found

A

ganglia
gastric, parietal and salivary glands

51
Q

Where are M2 muscarinic receptors found

A

heart
smooth muscle
autonomic nerve terminal

52
Q

Where are M3 muscarinic receptors found?

A

smooth muscle
gastric and salivary glands
vascular smooth muscle
bladder

53
Q

Where are M4 muscarinic receptors found?

A

auto- and heteroreceptors

54
Q

Where are M5 muscarinic receptors found?

A

generally low level expression but cerebral vascular smooth muscle

55
Q

Actions of the sympathetic nervous system

A

increase blood flow to skeletal muscle and decrease to GI
decrease GI activity
increase blood glucose
increase pupil size
increase heart rate and beat strength
decrease saliva but increase sweat excretion
increase bronchiole diameter

56
Q

what happens to the blood vessel or bronchiole diameter when the smooth muscle cells are excited/contracted - alpha1 receptors are activated?

A

excitation leads to contraction of the smooth muscle - decreased flow

decreased Alpha 1 adrenergic is excitatory - it also leads to an increase in intracellular calcium because it acts via Gq
A rise in IC calcium causes constriction - air flow / blood flow is decreased

57
Q

what happens to the blood vessel or bronchiole diameter when the smooth muscle cells are inhibited / relaxed - beta2 receptors are activated?

A

inhibition leads to relaxation of the smooth muscle which increases flow
also activation of beta 2 adrenergic receptors increases IC cAMP which is another signal for dilation - increased flow

58
Q

Alpha 2 receptors are located where and do what?

A

found at pre synaptic adrenergic terminals and inhibit neurotransmitter release - autoreceptors

also excite platelets to degranulate - clotting

59
Q

give examples of sympathetic and parasympathetic activity being:
independent
complimentary
antagonistic

A

independent: very little parasympathetic innervation of vascular smooth muscle, mostly sympathetic

complimentary: sex - PS causes erection, symp causes ejaculation

antagonistic: PS contracts pupils, symp dilates pupils

60
Q

Describe the reflex arc associated with orthostatic hypotension

A
  • person stands up and blood pools in their feet (gravity)
  • blood pressure drops
  • visceral receptors detect drop in blood pressure
  • afferent pathway sends signals to CV control centre in medulla oblongata
  • sympathetic activity increases and parasymp decreases
  • blood pressure increases
61
Q

Describe the baroreceptor reflex

A

stimulus = change in blood pressure
- baroreceptors at carotid artery and aortic arch send signals to medulla oblongata via glossopharyngeal and vagus nerve respectively (9 and 10)
- medullary neurons send signals to the parasymp neurons in the SA node, and sympathetic neurons in SA node, ventricles, veins, and arterioles

62
Q

What are sympathetic targets of CV centre in medulla oblongata in the baroreceptor reflex

A

SA node, ventricles, arterioles, veins

63
Q

What affects rate of baroeceptor firing?

A

The pressure in the carotid sinus (bulb after the common carotid splits) and the pressure in the aortic arch. They are stretch receptors.

64
Q

What receptor subtype is involved in hetero-inhibition of the:
- sympathetic by the parasympathetic
- PSymp by symp

A

parasymp blocks the symp with M4 musc receptors

sympathetic blocks parasymp with alpha2 adrenergic receptors

65
Q

How do the parasymp and symp NSs integrate their responses?

A

Hetero-inhibition of each system by the other

66
Q

What muscles control pupil diameter? What are their associated systems

A

circular muscles contract with Parasymp input onto muscarinic receptors and constrict the pupils

radial muscles constrict with symp input onto adrenergic (alpha1) receptors and pull open the pupil.

67
Q

What processes increase intraocular pressure?

A
  • Sympathetic input on lacrimal gland causes aqueous humor production
  • Also, net beta inactivation or alpha2 activation decreases cAMP and increases humour production
68
Q

What processes decrease intraocular pressure

A
  • parasympathetic input on ciliary muscle that constricts the pupil increases drainage from canal of Schlemm
    (reduced pupil size decreases resistance to outflow)
  • inhibiting cAMP formation (blocking beta R or activating alpha 2 Rs)
69
Q

Classes of agents used to treat open angle glaucoma
and three example drugs, one from each class

A
  • beta antagonists/ blockers
  • alpha 2 agonists
  • parasympathomimetics

timolol, apraclonidine, pilocarpine

70
Q

Actions of the parasympathetic nervous system

A

housekeeping - digesting, urinating, glandular secretion, energy conservation

  • decreases HR
  • constricts coronary vessels
  • constricts tissues in the lungs
  • dilates vasculature to visceral organs

PCL469 (18 decks)

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