ANS Flashcards
ANS
divided in sympathetic and parasymapthetic + enteric nervous system (GIT)
preganglionic
lightly myelinated slow conducting, thin, type B
conduction speed = 100 m/s
originates from the intermediolateral area of the grey horn from spinal regions:
T1 - T 12
L1 - L2
postganglionic
unmyelinated slow conducting, very thin, type C
conduction speed = 1 m/s
ganglion is collection of cell bodies outside of CNS.
denervation of autonomic nervous system
denervation hypersensitivity as up-regulation of NAChR receptors occurs and there is an exaggerated response to exogenous agonists.
primary organs ANS
viscera of thoracic and abdominal cavities
cutaneous blood vessels
sweat glands
piloerector muscles
SNS
originates in ventral/anterior horn and travels uninterrupted.
myelinated fast conducting type A alpha motor neurons. conducting 1000 m/s
denervation of SNS
flaccid paralysis and atrophy due to lack of innervation and activity at the muscle site
organisation of sympathetic nervous system
preganglionic originate at the intermediolateral area of grey horn. exit via the ventral roots and enter the sympathetic trunk via white ramus communicans.
synapse in the sympathetic trunk at the same spinal level and can then ascend or descend by entering para vertebral ganglion or passing to collateral ganglia.
postganglionic leave sympathetic trunk via gray ramus.
somatic neurons
monosynaptic
NT = ACh
receptor = Nicotinic 1 type
sympathetic neurons
cardiac tissue, smooth muscle and gland cells:
NT = NE
receptor = alpha and beta receptors
sweat glands:
NT = ACh
receptor = Muscarinic
Renal tissue:
NT = dopamine
receptor = dopamine 1
all preganglionic neurons
NT = ACh receptor = Nicotinic type 2
parasympathetic neurons
NT = ACh receptor = muscarinic receptor
block N1 type receptor
pancuronium is selective N1 type agonist and is used for general anaesthesia
block N2 type receptor
trimethaphan is selective N2 type agonist and blocks both arms of the ANS, used for treatment of hypertensive crisis
endocrine ANS neuron
adrenal meduall activation releases:
20% NE
80% epinephrine
NE endocrine release adds to effect of sympathetic stimulation on alpha and beta receptors
adrenal medulla enzyme
phenyl ethanolamine N methyl transferase converts NE into —–> epinephrine
epinephrine effects
epinephrine stimulates beta receptor to a greater extent.
epinephrine causes weak constriction of blood vessels.
epinephrine is 5 - 10 times more effective in stimulating metabolism.
vascular tone and denervation of the ANS
initially: marked increase in blood flow as vascular tone is lost
following days to weeks: vascular tone returns towards normal because of progressive increase in intrinsic tone of vascular muscle.
following test doses of NE: the response of vessels to NE (constriction) can increase 3 to 4 fold due to upregulation of receptors at denervation site.
organs with only sympathetic innervation
kidneys, liver, arterioles and veins, piloerection and sweating
beta1 adrenergic receptors only
heart + kidneys
alpha receptors only
eyes, endocrine pancreas, exocrine pancreas, sex organs
both alpha and beta receptors
arteries and veins, salivary glands, stomach, urinary bladder
alpha 1 receptor activation
always contraction in its target areas
vascular smooth muscle of skin, splanchnic region, sphincters of the GIT and urinary tract, radial muscle of the iris.
NE binds to alpha 1 receptor triggering a conformational change in the GqPCR at the membrane. the alpha q subunit is inactive when bound to GDP.
conformational change of GPCR causes alpha q subunit to bind to GTP and be released into the cytosol.
alpha q bound to GTP interacts with phospholipase C triggering the activation of PIP2.
PIP2 allows the liberation of diacyclgycerol and IP3.
IP3 activates calcium release from ER/SR.
diacyglycerol in the presence of calcium will activate protein kinase C.
protein kinase C has a major role in phosphorylating various proteins in the cell.
beta receptors
beta1 receptor activation in SA node causes heart rate increase and increase in contractility of the heart, renin secretion in the kidney.
NE binds to beta receptor causing a conformation change in GsPCR at the membrane.
alpha s subunit is inactive when bound to GDP and becomes active and released when conformational change occurs and bound to GTP.
alpha s bound to GTP will phosphorylate adenyl cyclase.
phosphorylated adenyl cyclase converts ATP to cAMP (second messenger).
cAMP activates protein kinases and induces downstream changes.
nicotinic AChR
ligand gated with ion channel (for potassium out, sodium in) as part of the receptor itself.
always excitatory
muscarinic AChR
GPCR. binding to muscarinic receptor causes conformational change in membrane proteins which in turn affects release
longer lasting effects and can be both excitatory or inhibitory
excitatory: (smooth muscle of digestive tract)
causes contraction when potassium channels close and sodium channels open allowing depolarisation
inhibitory: (slow heart rate) causes relaxation (produces slower heart rate) when potassium channels open i.e. hyperpolarisation.
non adrenergic non cholinergic @ sympathetic axon
3 phases of response: (contraction)
1. ATP binds to P2X purinoceptor (ligand gated cation channel) and causes calcium and sodium to enter the cell causing depolarisation and activation of another voltage gated calcium channel causing rapid phase of contraction
- NE binds to alpha 1 adrenoceptor and Gq/PLC/IP3 cascade results in calcium release from ER/SR causing second phase of contraction
- neuropeptide Y binds to Y1 receptor and causes slowest calcium increase producing the slowest phase of contraction.
non adrenergic non cholinergic @parasympathetic axon
the parasympathetic axon releases:
ACh
NO
VIP (vasoactive intestinal peptide)
2 phases of response: (relaxation)
1. NO is released by the neuron into smooth muscle cell.
ACh is also released by the neuron which acts on M3 receptors on endothelial cell to produce NO also which will diffuse into smooth muscle cell.
both sources of NO activate guanylyl cyclase and raise cGMP in smooth muscle cell contributing to the first phase of relaxation.
- neuropeptide VIP binds to receptors on smooth muscle cell causing an decrease in calcium also which contributes to the second (delayed) phase of relaxation.
vasoactive intestinal peptide
is released along with ACh by sympathetic nerves to sweat glands and by parasympathetic nerves to enteric nervous system.
cGMP inducing smooth muscle relaxtion
3 mechanisms:
1. inhibits calcium entry into the cell and decreases intracellular calcium concentrations
- activated potassium channels which leads to hyperpolarisation and relaxation.
- stimulates cGMP dependent protein kinase which activates myosin light chain phosphatase (an enzyme that dephosphorylates myosin light chains)
peripheral nervous system
function: communication between CNS and rest of body
includes the ANS + SNS
31 spinal nerves carry info to and from spinal cord
12 cranial nerves carry info to and from the brain
enteric nervous system
includes the myenteric and submucosal plexuses in the wall of GIT
myenteric plexus regulates motility
submucosal plexus regulates ion + water transport and secretion
functions of the ANS
- Maintenance of homeostasis (blood pressure)
- integration of stress response
- integration of visceral function (food digestion)
overactive bladder case study
parasympathetic antagonist (muscarinic cholinergic antagonist) specifically M3 which mediates bladder contractions are useful.
sympathetic agonist at alpha 2 receptors to inhibit bladder contraction would have a small effect. sympathetic alpha 1 agonist would inhibit urination but the urge to urinate would still be present.
