The Parasympathetic Nervous System Flashcards
PSN effects on the heart?
The parasympathetic nerve to the heart (vagal nerve):
Decreases force of contraction
Reduces heart rate
The vagus has a more limited distribution than the cardial accelerator nerves in the sympathetic system
They are found mainly innervating the sinoatrial node, the atrial ventricular node and the atria
When you stimulate the vagus nerve the height of this action potential i.e. how depolarised it gets, reduces considerably.
Moreover the resting membrane potential becomes more negative/ it hyperpolarises
In addition we can also see a reduction in the frequency of contraction
PSN effects on blood vessels?
Acetylcholine produces considerable vasodilatation to systemic arteries but there is far less parasympathetic innervation to arteries
This happens only if acetylcholine can get to an artery as it is broken down by choline esterase
PSN effects on male genitalia aka pps?
One atrial bed with rich parasympathetic innervations- the penis
Stimulation of parasympathetic nerve results in the dilation of penile artery engorgement of corpus cavernosum
PSN effects in non-vascular smooth muscle?
Parasympathetic nerve activation causes contraction
The key ones are:
Bladder detrusor-causes urine to flow out
Airway- acetylcholine released from these nerves produces bronchoconstriction/ bronchospasm
Gastrointestinal tract-there is both a longitudinal layer and a circular layer of smooth muscle in our GI tract and acetylcholine will produce considerable contraction of these muscles.
Also the uterus
PSN effects on eyes?
Contracts circular muscle causing the pupils to narrow
Contracts from left to right
Contraction of ciliary muscle
Relaxes suspensory ligaments
Allows lens to bulge
And therefore light coming from a close structure will be focused on the retina
What effect do the parasympathetic nerves have on secretions?
The parasympathetic nerves have a considerable effect in promoting various secretions including:
Saliva
Gut acid- where it has a direct effect on the parietal cells producing the acid and cells that make histamine which then stimulates the parietal cells
Tears
Sweat (a sympathetic effect)- acetylcholine also increases sweating
How do cholinergic neurones perform their function?
Choline gets taken up by a sodium-choline transporter, a symporter, then combines with acetyl coenzyme A through the enzyme choline acetyl transferase to produce acetylcholine
It is then packaged into vesicles, sometimes by itself, sometimes with other agents such as vasointestinal polypeptides (VIP)
The influx of calcium following the depolarisation of the nerve terminal causes the SNARE proteins on the vesicle to interact and fuse with the membrane
What compounds inhibit acetylcholine esterase?
Neostigmine
Physostigmine
Edrophonium
Parathion (insecticide)
What are the different cholinoceptors and what part of the body do they influence?
N1 or Nm- Skeletal muscle
N2 or NN- Autonomic ganglia, CNS
M1- CNS, peripheral neurones, gastric parietal cells
M2- Atria, SAN, SVN
M3- Visceral smooth muscle, secretory glands, endothelial cells
M4 and M5- CNS
With muscarinic receptors, the odd numbers are coupled to phospholipase C while even ones are negatively coupled with adenylate cyclase meaning they decrease cAMP.
What are the agonist and antagonist of the different PSN neurones?
Selective agonists include:
Nicotinic-Nicotine, Lobeline
Muscarinic-Muscarine, bethanechol, Pilocarpine
Selective antagonists include:
Nicotinic-Tubocurarine, hexamethonium, Pancuronium
Muscarinic-Atropine, hyoscine, Pirenzepine, Ipratropium
What are nicotinic acetylcholine receptors and how do they work?
Activation of nicotinic acetylcholine receptors was covered in receptor mechanisms I
Ach binding produces a conformational change that opens channel pore
Allows influx of cations (Na or Ca)
Produces an Excitatory Junction Potential in the target cell either in the CNS, the post-ganglionic fibre of the ANS and also on the skeletal muscle
Effect terminated by unbinding of Ach
How are M2 receptors activated in the SAN and atria?
The M2 receptor is negatively coupled with adenylate cyclase so its reducing the level of cAMP which means we have less activation of the pacemaker conductants in the heart
So the pacemaker is less active and that will result in a slower heart rate.
There’s less PKA so the calcium channels are reduced, less sensitive to membrane voltage, and also the release of calcium from the SR is also less effective.
This will work to bring down the force of contraction and rate of contraction.
IN ADDITION
In the heart the beta-gamma subunits activate a potassium channel the activation of potassium causes the membrane potential to hyperpolarise and that will limit activation
What does the M3 receptor do and how is it activated?
Contracts non-vascular smooth muscle in particular:
GI tract
Bladder
Airways
Uterus
Iris (eye)
Activation of M3 receptors leads to increased activation of Phospholipase C and calcium release
Here is the M3 receptor, a G-protein coupled receptor with 7 transmembrane domains.
This one is coupled to Gq/G11 proteins
These, when activated, turn on phospholipase C, its substrate PIP2 gets cleaved into DAG and IP3
IP3 diffuses to the internal calcium storage, binds to it receptor and releases calcium
Calcium stimulates Myosin light chain kinase and you get contraction
Why does the activation of M3 receptors in arteries relax them?
This is because in the blood vessel, the muscarinic receptors are on the smooth muscle layer but rather heavily expressed in the endothelium
The endothelium cannot contract as there are no contractile proteins but what it does have is an enzyme called NO synthase which makes nitric oxide with the starting material arginine
So arginine gets converted to nitrous oxide which diffuses rapidly to our contracted smooth muscle and it makes it relax
How does activation of M3 receptors cause increased secretions?
Through increased phospholipase C and increased calcium release it causes saliva to be produced and secreted (some M1 receptors can also help)
Tears are also increased
Down in the gut there are M3 receptors on the cells that make gut acid called parietal cells but there are also M3 receptors along with M1 on cells that store histamine called enterochromaffin cells, and histamine is a big stimulant of gut acid.
There are M3 receptors on our sweat glands
