8 - Overview of Peripheral Nervous System

Question 1

What are the two main divisions of the peripheral nervous system? How are they organized?

Answer 1

Sensory and motor pathways.

Motor pathways are divided into autonomic and somatic nervous system.

Autonomic is divided into sympathetic and parasympathetic.

Question 2

How do the autonomic and somatic motor nerves differ? What is the site of communication called?

Answer 2

Autonomic: pregang. neurons relay (synapse) in autonomic ganglia and have effector organs of heart, smooth muscle, and exocrine glands (neuroeffector junction)

• Ach is pregang nt
• post can be Norepi or Ach

Somatic motor: single neural network, cell bodies within the spinal cord and directly innervate skeletal muscle at the neuromuscular junction (Ach).

Question 3

What is the anatomical difference between the ratio of segment lengths and the degree of divergence in sympathetic vs parasympathetic nerves?

Answer 3

Sympathetic have short pregang and long postgang while parasympathetic have long pregang and short postgang.

Sympathetic have high divergence (1:30 pre:post), while parasympathetic have low divergence (1:#).

Question 4

What is the anatomical difference between extent of effects and nerve function in sympathetic vs parasympathetic nerves?

Answer 4

Sympathetic effects are widespread while parasympathetic effects are highly localized.

Both sympathetic and parasympathetic nerves can be excitatory or inhibitory.

Question 5

What is the function of somatic motor nerves?

Answer 5

Innervate skeletal muscle and produce movement.

Question 6

How do sympathetic and parasympathetic nerves differ in activity?

Answer 6

Sympathetic are normally continuously active and their degree of activity varies from moment to moment and by organ. Can also discharge as a unit.

Parasympathetic: organized for discrete local discharge. Concerned with maintenance of organ function during periods of minimal activity.

Question 7

Otto Loewi

Answer 7

Nerves store things that are released when stimulated to cause an effect.

Determined that this substance was acetylcholine for the vagus nerve.

Determined it was Norepinephrine to cause increased HR.

Question 8

What are the steps involved in neurotransmission?

Answer 8

Depolarization causes Calcium channels to open and calcium to flow in.

This causes fusion of the synaptic vesicles with the membrane and then a family of proteins fuses and allows the release of contents into the cleft.

Response of postsynaptic neuron can be excitatory or inhibitory.

Question 9

What are the neurotransmitters used for peripheral nerves for skeletal muscles and smooth muscle cardiac muscles and glands? What receptors are associated with each?

Answer 9

Skeletal muscle: Ach via nicotinic receptors

Autonomic parasympathetic: Preganglionic use Ach, and postganglionic use Ach via muscarainic receptors.

Autonomic sympathetic: Preganglionic use Ach, postganglionic use usually Norepi (adrenergic receptors alpha/beta) but sometimes Ach (muscarinic, sweat glandS).

Question 10

Sympathetic NS can also stimulate _____ _____ with Ach to cause the release of 80% epinephrine and 20% Norepinephrine.

Answer 10

Adrenal medulla.

Question 11

How is Acetylcholine synthesized? How and where is it degraded?

Answer 11

AcetylcoA and Choline make acetylcholine via the enzyme acyltransferse.

Ach degraded in the synaptic cleft by acetylcholine esterase which is the reverse of the synthesis reaction. This is a very efficient reaction.

Question 12

What is the action of botulinum toxin?

Answer 12

It gets into the nerve terminal and cleaves proteins during the tethering process and prevents release of Ach into the cleft.

Causes flaccid paralysis.

Question 13

What are the types of cholinergic receptors? What does cholinergic receptor mean?

Answer 13

Nicotinic and muscarinic.

Receptor for Acetylcholine.

Question 14

What are the three classes of nicotinic receptors? What type of receptors are these? What is the response?

Answer 14

Ganglionic: found on neurons (NsubN)
Skeletal muscle: NsubM for muscle
Neuronal CNS

These are ligand gated ion channels. Ligand binding causes excitatory response.

Question 15

What are the types of muscarinic receptors? What type of receptors are these?

Answer 15

M1, M2, M3, M4, M5.

All part of GPCR superfamily that activate heterotrimeric G proteins.

Question 16

What is the structure of nicotinic receptors?

Answer 16

Five subunits: two alphas, a beta, delta, and gamma.

Alpha is where Ach binds to open up cation channels that cause depolarization of the membrane.

Question 17

What is the structure of muscarinic receptors?

Answer 17

Bind and activate heterotromeric G proteins that modify signaling pathways.

Question 18

What is the location, response, and molecular mechanism of muscle Nm nicotinic receptors?

Answer 18

Located at the neuromuscular junction

Response: End-plate depolarization and increased cation permeability that causes skeletal muscle contraction

Question 19

What is the location, response, and molecular mechanism of Peripheral neuronal
Nn Nicotonic receptors?

Answer 19

Located in autonomic ganglia and adrenal medulla.

Causes depolarization and firing of post-ganglionic neuron or depolarization and secretion of catecholamines both via increased cation permeability.

Question 20

What is the location, response, and molecular mechanism of central neuronal (CNS) nicotinic receptors?

Answer 20

Located in the brain and spinal cord.

Controls neurotransmitter release via increased cation permeability.

Question 21

What G protein family do muscarinic receptors M1, M3, and M5 belong to? What is their response and molecular effect?

Answer 21

Gq protein family.

depolarization and excitation. Activates phospholipase C.

Question 22

What G protein family do muscarinic receptors M2 and M4 belong to? What is their response and molecular effect?

Answer 22

Hyperpolarization and inhibition.

Inhibites AC by decreasing cAMP, activate K+ channels (hyperpolarization), Inhibit voltage-gated Ca2+ channels.

Question 23

What is the pathway by which Norepinephrine is made?

Answer 23

Tyrosine converted to DOPA by tyrosine hydroxylase.

DOPA converted to dopamine via L-aromatic amino acid decarboxylase.

Dopamine to norepinephrine via dopamine-B-hydroxylase.

Question 24

How is epinephrine made?

Answer 24

Norepinephrine is converted to norepinephrine by Phenethanolamine-N-methyltransferase in the adrenal medulla.

Question 25

Where is norepi made and stored?

Answer 25

Tyrosine is transported into the presynaptic terminal and made into dopamine.

Dopamine taken up into a storage vesicle called VMAT2 where its made into norepi and stored.

Question 26

What happens when norepi is in the synaptic cleft? How is it removed?

Answer 26

Works on alpha and beta receptors in the cleft.

90% removed by being taken back up by NAT and goes back into storage granules.

5% diffuses away

5% taken away by effector cell transported to be metabolized.

Question 27

What is the action of the drug Reserpine?

Answer 27

It inhibits VMAT transporters so less norepinephrine is stored and therefore less is released.

Used as an antihypertensive.

Question 28

What is the action of cocaine?

Answer 28

Inhibits norepinephrine transporter and therefore prevents norepi from being taken up.

More norepi is therefore in the cleft and causes euphoric effects and vasoconstriction.

Question 29

What is the function of presynaptic alpha2 receptors?

Answer 29

These are autoreceptors: when norepi is in the cleft it can act on them and produce feedback inhibition of norepi release.

It does this through inhibition of Ca and a decrease in cAMP.

Question 30

What are two enzymes that are involved in the metabolism of catecholamines? What mechanisms does each use?

Answer 30

Monoamine oxidase: oxidatively deaminate catecholamies. Located in the mitochondria. In adrenergic nerve terminals, but also liver and kidneys.

COMT: catechol-O-methyltransferase; cytosolic enzyme in high levels in the liver and kidneys. Transfers a methyl group to the 3-hydroxy position.

Question 31

What are the types of adrenergic receptors? What is their structure?

Answer 31

All GPCRs.

There’s alpha and beta receptors.

alpha one and alpha two.

Beta one, two, and three.

Question 32

Nearly all postganglionic sympathetic nerves use ______ and respond with alpha or beta receptors.

Answer 32

Norepinephrine.

Question 33

What is the location, response, and most common molecular effector system involved in alpha 1 adrenergic receptors?

Answer 33

Gq.

Located in vascular and other smooth muscle and glands.

Response is contraction and secretion from glands.

Activates phospholipase C which cleaves PIP2 into IP3 and DAG.

Question 34

What is the location, response, and most common molecular effector system involved in alpha 2 adrenergic receptors?

Answer 34

Gi

Located in nerve terminals, glands, vascular smooth muscles.

Decreases norepi release, decreases sexcretion, and causes smooth muscle contraction.

Inhibits AC and decreases cAMP.

Question 35

What is the location, response, and molecular effect of beta 1, 2, and 3 adrenergic receptors?

Answer 35

All use the Gs protein family.

B1: cardiac muscle and glands
B2: vascular and other smooth muscle, skeletal muscle, and liver
B3: adipose tissue

Increased cardiac contraction, increased secretion, relaxation of smooth muscle, lipolysis, glycogenolysis.

All of them work by activate AC.

Question 36

What does sympathetic innervation cause arteries and veins to do in most cases?

Answer 36

Contract to increase venous return.

This is done through the Gq heterotrimeric G protein.