Lecture 2 - Parasympathetic NS

Question 1

What are the main targets of parasympathetic nervous system activity? (Think general) .

Answer 1

Smooth muscle

Cardiac muscle

Glands (stomach, eyes, mucus ducts, etc..)

Question 2

What are the primary effects of parasympathetic nervous system activation?

Answer 2

SLUDGE BB + PPP

Salivation

Lacrimation

Urination

Digestion

GI motility activity

Emesis

Bronchospasm

Bradycardia

Also pupillary constriction, perspiration, paralysis

Question 3

What is the main parasympathetic NS nerve that innervates thoracic and abdominal structures?

Answer 3

The Vagus (“wandering”) nerve

Question 4

What sensory and motor innervation does the “wandering” nerve provide?

Answer 4

Motor /sensory innervation to all nerves of the larynx except the cricothyroid (superior laryngeal)

Damage results in hoarse voice. Bilateral damage results in stridor and laryngeal obstruction.

Also innervates many thoracic and abdominal structures - it is central to the parasympathetic NS and is one reason why parasymp effects are so global.

Question 5

What is the main neurotransmitter that mediates the effects of the parasympathetic nervous system?

Answer 5

Acetylcholine (acetyl co-a + choline)

Question 6

Briefly describe storage and release of ACh by the presynaptic neuron.

Answer 6

Acetyl Co-A = intracellular mitochondrial product (think cellular respiration)

Choline = reuptaken from degraded ACh from extracellular space by high affinity sodium-choline pump (which is coupled to an Na/K ATPase pump)

Acetyl CoA is combined with Choline and packaged into vesicles.

Vesicle is released into synaptic space by Ca++ cascade (which results from depolarization) and botulinum.

Question 7

Botulism: what is it and what are its effects? Why?

Answer 7

Botulism is a rare food-borne illness that results in flaccid paralysis and possible respiratory failure.

Can also be wound-borne (more common in substance abusers with open wounds and poor hygiene).

The bacteria releases a deadly toxin (botulinum toxin A) that binds to vesicles and prevents exocytosis - it acts like a botulinum receptor antagonist.

Question 8

Describe how ACh activity is terminated.

Answer 8

> Reuptake by presynaptic cell

> Hydrolysis into acetate and choline, accelerated by acetylcholinesterase and pseudocholinesterase (AKA butyrlcholinesterase - exists in much lower amount but helps break down ACh in the bloodstream)

Question 9

Cholinesterase inhibitors we may encounter in the clinical setting:

Answer 9

Neostigmine

Edrophonium

Physostigmine

Pyridostigmine

Question 10

What are the two large classes of receptor subtypes of the parasympathetic nervous system?

Answer 10

Nicotinic ACh receptors

Muscarinic ACh receptors

Question 11

Where are nicotinic receptors loated?

Answer 11

At every NMJ and autonomic ganglia (so global nicotinic AChR activation, like in nicotine intake, results in both parasympathetic and sympathetic activity).

Question 12

What kind of receptors are nicotinic receptors and what is the molecular effect of their stimulation?

Answer 12

Nicotinic AChRs = ligand-gated ion channels.

Activation leads to membrane permeability to Na+ and K+ –> depolarization

Question 13

There are at least 5 subtypes of muscarinic receptors. What are the 3 that we examine more often?

Answer 13

M1

M2

M3

Question 14

Where are M1-3 type muscarinic receptors distributed?

Answer 14

M1 - autonomic ganglia and CNS

M2 - supraventricular cardiac cells (mediates brady and decreased contractilty)

M3 - smooth muscles and glands

Question 15

What are the immediate molecular effects of muscarinic AChR activation?

Answer 15

Release for Ca++ from the sarcoplasmic reticulum from G-protein coupled transduction (Phospholipase C –> IP3 and DAG)

This ultimately leads to NT release.

Question 16

Does activation of muscarinic receptors lead to vasoconstriction? Why or why not?

Answer 16

No.

ACh release at muscarinic receptor sites leads to increased nitric oxide release by endothelial clls in smooth muscles which leads to focal vasodilation.

If endothelial cells are not present, then it would lead to smooth muscle constriction (but this is not the caese).

Question 17

Does activation of muscarinic receptors lead to increased cardiac contractility and conduction?

Answer 17

No.

M2 muscarinic cells are at the cardiac system.

M2 receptors inhibit cardiac cells (slower contractions and conduction rate) by initiating a G-protein cascade that leads to increased hyperpolarization of cardiac cells and thus, slower depolarization speed