PPT 6- ANS & Sympathetic transmission Flashcards
Exam 2
What is the afferent pathway, and what information is sent?
going towards CNS
a) special sensory receptors - 5 senses, except touch
b) somatic sensory receptors - skin, skeletal muscle, pressure, pain
c) visceral sensory receptors - internal organs
What is the efferent pathway, and what information is sent?
going away from CNS
a) somatic nervous system - conscious control
b) autonomic nervous system - smooth muscle, cardiac muscle, glands. (parasympathetic and sympathetic NS)
c) enteric nervous system
What is the somatic nervous system?
part of the peripheral nervous system that controls voluntary movement
Where are neuron cell bodies for the somatic system located?
in the CNS
has axons that leave the CNS, but cell bodies are in the CNS
Where are neuron cell bodies of the autonomic system located?
outside the CNS (ganglia)
What are the subdivisions of the autonomic nervous system?
sympathetic, parasympathetic, and enteric
What is the enteric system?
primitive system, gut feeling
What is the nerve that is important for regulating cardiac function?
vagus nerve (CN X)
Chain ganglion are present in which NS? parasympathetic or sympathetic?
sympathetic
Where do sympathetic axons leave the CNS?
Thoracolumbar region
What are sympathomimetic drugs?
Mimic the effects of NE binding to receptors
Sympathetic NS postganglionic fibers release which neurotransmitter?
NE, skeletal muscles and sweat glands release ACh
For sympathetic NS, preganglionic fibers are ________, while postganglionic fibers are _________.
preganglionic= short
postganglionic= long
For parasympathetic NS, preganglionic fibers are ________, while postganglionic fibers are __________
Preganglionic= long
postganglionic= short
Where do parasympathetic axons leave the CNS?
Craniosacral regions.
Most from brainstem, bladder and genitals from sacral
Sympathetic NS preganglionic fibers release which neurotransmitter?
ACh
Which drugs are direct acting sympathomimetics?
Epinephrine, isoproterenol, albuterol
Which drugs are indirect acting sympathomimetics?
ephedrine and amphetamines
don’t bind directly to receptor, but block the reuptake of NE or reverse the NET, leaving NE in the synapse longer
What effects are seen from sympathomimetics?
Vasoconstriction
Increased inotropic and chronotropic effects
Decrease bronchiole tone
Decreased uterine muscle tone
What are sympatholytics?
drugs that inhibit the sympathetic nervous system
alpha/beta blockers
What effects are seen from sympatholytics?
vasodilation, decreased BP
decreased chronotropy (heart rate)
Which muscarinic receptors are excitatory?
M1, M3, M5
Which muscarinic receptors are inhibitory?
M2, M4
What neurotransmitter(s) acts on cholinergic receptors?
ACh
What neurotransmitter(s) acts on adrenergic receptors?
epinephrine and norepinephrine
How many types of alpha receptors are there?
2
alpha 1
alpha 2
How many types of beta receptors are there?
3
beta1, heart
beta2, lungs
beta3, fat tissue
How many types of dopamine receptors are there?
5
D1-5
Which alpha receptors are stimulatory and what does it activate?
alpha 1, activates Gq protein, activates phospholipase C which activates secondary messengers IP3 and DAG
which alpha receptors are inhibitory and what does it inhibit?
alpha 2, inhibits adenylyl cyclase; leads to decreased cAMP
Where is the ganglia located in the sympathetic NS?
Close to the spinal cord
Where is the ganglia located in the parasympathetic NS?
In the visceral effector organs
The enteric NS is mainly under _____ control
parasympathetic
Sympathetic input mainly inhibitory
Many neurons in the enteric NS are mostly _____
non-adrenergic, non-cholinergic (NANC)
What are the effectors of the ANS vs somatic?
ANS - cardiac muscle, smooth muscle, and glands (not skeletal)
Somatic - skeletal muscle
Axons of the ANS are a ___-neuron chain
2
- The preganglionic (first) neuron has a lightly myelinated axon
- The ganglionic (second) neuron extends to an effector organ
In the skeletal muscle, there are ____ ganglion
no
In the ANS, the preganglionic fibers release ____, while postganglionic fibers release ____
ACh
NE or ACh
Parasympathetic NS mostly releases what neurotransmitter?
ACh
The sympathetic NS mostly releases what neurotransmitter?
NE, some ACh (sweat glands)
Sympathetic drugs that mimic the sympathetic nervous system are called _____
Sympathomimetics
Albuterol directly acts on what?
beta receptors in lungs
Sympathomimetics are taken up by ____
NET (NE transporter)
Ionotropic is ____ chronotropic is ____
Force, rate
Propranolol
Beta selective sympatholytic
Phentolamine
Alpha selective sympatholytic
Labetolol
Mixed selective sympatholytic
Are Beta receptors inhibitory or stimulatory?
All beta receptors are stimulatory - stimulates adenylate cyclase, increasing cAMP
What are the types of cholinergic receptors?
Muscarinic and nicotinic
What type of receptors are muscarinic receptors?
GPCRs
What type of receptors are nicotinic receptors?
Ion channels
What are the adrenergic receptors? What do they respond to?
Alpha, beta, dopamine
NE
What are the 2 nicotinic receptor subtypes in the PNS? Where are they located?
Neuronal (occurs at ganglion)
Muscular (occurs skeletal muscle endplates)
Where are dopamine receptors located?
mostly in brain, some in smooth muscle, CV, and kidneys
What is the GPCR that alpha 1 activates? Effector?
Gq/G11 - activates phospholipase C
What is the GPCR that alpha 2 activates? Effector?
Gi - inhibits adenylate cyclase
What is the GPCR that beta activates? Effector?
Gs - stimulates adenylate cyclase
Where are alpha 1 receptors primarily found?
in the smooth muscle cell that surrounds the blood vasculature
How does IP3 work to increase BP?
- IP3 opens Ca++ channels from sarcoplasmic reticulum → releasing Ca++ into cell
- Ca++ in smooth muscle cell activates enzymes MLCK → MLCK phosphorylates myosin → contraction of smooth muscle cell → increased BP
How does DAG work to increase BP?
DAG activates protein kinase C (PKC) → Ca++ sensitization → inhibits MLCP (removes phosphate from myosin) → more active myosin → contraction → increase BP
How does the activation of beta receptors work in the heart?
NE activates beta receptors - G stimulatory → stimulates adenylyl cyclase → increases cAMP → activates PK-A → more ICF Ca++ (from ECF and from sarcoplasmic reticulum) → contraction
How does the activation of beta 2 receptors work in the peripheral muscle?
NE binds to B2 in periphery → Increases cAMP → inhibit MLCK → no active myosin → relaxation - allows peripheral vessels to dilate
Describe the negative feedback loop of NE
NE in the synapse for a prolonged period will inhibit further NE release by binding to alpha 2 on the cell that released it - keeps heart from working too hard
What are the primary sympathetic receptors?
Alpha and beta
What are the primary parasympathetic receptors?
Cholinergic receptors
_____ causes dilation of skeletal blood vessels, whereas ____ causes constriction of the blood vessels in the abdominopelvic cavity
ACh, NE
Skeletal muscle blood vessels are innervated by
ACh postganglionic fibers of the sympathetic division - dilation
Describe how the autonomic feedback loop works to lower an increase in MAP
Baroreceptors sense increased pressure on arteries → notifies CNS vasomotor center → activate PANS → ACh release → decrease HR and CO→ MAP back to normal
Describe how the autonomic feedback loop works to raise a decrease in MAP
Decrease in MAP → baroreceptors sense this → notifies CNS vasomotor center → activates SNS → NE binds to alpha and beta 1 receptors → increases MAP
- beta 1 receptors in heart (increase HR and CO)
Increases contractile force
- alpha receptors in peripheral vasculature (increasing blood return to heart)
Increases venous tone
Describe how the hormonal feedback loop responds to a decrease in MAP in the RAA system
MAP too low → kidney senses in tubules (juxtaglomerular apparatus) → releases renin → activates angiotensin cascade (can restrict blood flow directly or go to adrenal cortex) → increases aldosterone production → take up more water in blood volume, produce less urine → increased venous return → increased SV → increased CO → increased MAP
What is a heteroreceptor?
A receptor on the neuron that responds to something that the neuron isn’t releasing (releases epi and receptor for ACh, slows down the release of epi)
What is an autoreceptor?
A receptor that responds to the same neurotransmitter that is being released (epi and epi)
Can be inhibitory (negative feedback) or excitatory (positive feedback)
What are the mechanisms for presynaptic regulation feedback control?
Herteroreceptors and autoreceptors - receptors on the cell releasing neurotransmitters
Compare the SNS vs PANS of the SA node and which receptors are present
SNS: accelerates SA node - B1 and B2
PANS: decelerates the SA node - M2
Compare the SNS vs PANS of the heart contractility and which receptors are present
SNS: increases heart contractility - B1 and B2
PANS: decreases heart contractility - M2
Compare the SNS vs PANS of bronchiolar smooth muscle and which receptors are present
SNS: relaxes bronchiolar smooth muscle - B2
PANS: contracts bronchiolar smooth muscle - M3
Compare the SNS vs PANS of the blood vessels and which receptors are present
SNS:
- alpha: vasoconstriction of smooth blood vessels → dominant effect
- beta and cholinergic - vasodilation of arterioles in skeletal muscles
PANS: vasodilation of GI tract, genitalia, and salivary glands; little effect on total peripheral resistance - M3
At rest, skeletal muscles take up ___% of circulating blood flow
20%
During physical activity or sympathetic stimulation, skeletal muscles take up to ___% of circulating blood flow
80&
Differentiate between cholinomimetics, parasympatholytics, sympathomimetics, and sympatholytics
Cholinomimetics (Parasympathomimetics) - mimic the effects of ACh
Parasympatholytics (Antimuscarinics) - Block effect of PANS
Sympathomimetics - Mimic effect of SNS
Sympatholytics (α-blockers, β-blockers) - Block SNS
The ____ is the gap between the neuron and the cell
synapse
List three types of synapses
- Electrical (gap junctions)
- Chemical
- En passant (place other than axon terminal)
The synapse is the target for many drugs, including
Sleep modulators, general anesthetics - CNS
CV - PNS
What is the role of the neuron?
Sends AP from neuron cell body to the telodendria (endpoints) capped with synaptic boutons (where neurotransmitters are stored)
info is coming into neuron through the _____
Dendrites
Action potentials are generated in the ________
axon hillock
What are the types of synapses?
Chemical - neurotransmitters
Electrical - Gap junctions
After nurotransmitters are released, they are either
Broken down by enzymes and/or taken up into presynaptic cell
What are En Passant Synapses?
- Axon has swellings that can release neurotransmitters in some neurons
- Additional synapses between cells
- One neuron can effect multiple different effectors
Describe the main stages of synaptic transmission
What are the 4 possibilities of neurotransmitter fate?
All decrease neurotransmitter in synapse
1. Diffuses away from synapse
2. Degraded by enzymes
3. Uptake into pre-synaptic cell
4. Uptake into surrounding cells
What are the 6 Neurotransmitter Classes?
- Esters
- Monoamines
- Amino Acids
- Purines
- Peptides
- Inorganic gases
Give an example of an ester neurotransmitter
Acetylcholine (ACh)
Give an example of a monoamine neurotransmitter
NE, Serotonin, Dopamine
Give an example of an amino acid neurotransmitter
Glutamate, GABA, glycine
Give an example of a purine neurotransmitter
Adenosine, ATP
Give an example of a peptide neurotransmitter
Substance P, Endorphins - mediate pain and analgesia
Give an example of a inorganic gas neurotransmitter
Nitric oxide (NO)
NO is different than other neurotransmitters because it is not ______
stored - made as needed by nitric oxide synthase
Compare the speed of nicotinic vs muscarinic receptors
Nicotinic - Ion Channel - FAST (NMJ)
Muscarinic - GPCRs - slower
Monamines are released by
Adrenergic Fibers
All human emotions can be boiled down to which 3 neurotransmitters?
NE, dopamine, and serotonin
Lovheim Cube of Emotion
If deficient in any of these in CNS, can’t fell full range of emotions
How do SSRIs work to treat depression?
Prevent re-uptake of serotonin, allows serotonin to stay in synapse longer
What is the most important excitatory neurotransmitter in brain?
Glutamate
What are the inhibitory neurotransmitters in brain?
Glycine and GABA
Differentiate between excitatory and inhibitory neurotransmitters
- Excitatory neurotransmitters cause depolarizations (e.g., glutamate)
- Inhibitory neurotransmitters cause hyperpolarizations (e.g., GABA and glycine)
What happens at a cholinergic synapse?
- Starts from an AP coming from the axon hillock in the neuron → travels down the axon to terminal bouton → terminal bouton becomes depolarized
- Ca influx into terminal and binds to vesicles that bind to the surface of the cell, destabilizes storage vesicles → release of ACh into the synaptic cleft (exocytosis)
- ACh binds to receptors, opening Na channels and depolarizing post-synaptic cell → increase in Ca++
- ACh broken down by AChE
Describe the formation and transport of ACh
- ACh made in the cytoplasm of the cell that is releasing it
- Transported into vesicles
What is the name of the enzyme that creates ACh? Where is it found?
Choline acetyltransferase (ChAT) - found inside the neuron
What is the name of the enzyme that breaks down ACh? Where is it found?
Aceytlcholinesterase (AChE) - found in the synapse
Breaks down ACh into Acetic acid and choline
What are the transport molecules for ACh?
CHT – choline transporter into neuron - co-transporter with Na via facilitated diffusion
VAT – transports ACh into vesicle
What are the components of the anchoring/docking portion of the cholinergic transmission?
SNARE Complex - Syntaxin and SNAP-25 - anchor vesicles near release site
VAMP - vesicular associated membrane protein, a part of the synaptic membrane
What is the Ca++ sensor in the anchoring/docking portion of the cholinergic transmission?
Synaptotagmin - Binds to calcium during efflux → facilitates rapid exocytosis
What are the 4 steps of cholinergic transmission?
Transport, anchoring/docking, priming, and fusion
The priming portion of cholinergic transmission is
- ATP dependent
- Supports rapid exocytosis
The fusion portion of the cholinergic transmission is
Calcium-induced (synaptotagmin)
- Fusion of membrane (fast)
- Fusion pore
What are the 5 cholinergic Inhibitors?
- Hemicholiniums – CHT
- Block choline transport (not therapeutic drug, experimental research)
- Vesamicol – VAT
- Block acetylcholine transporter (research)
- Calcium channel blockers – Voltage gated calcium channels
- Decreasing HR and BP
- High levels of calcium channel blockers can inhibit neuron transmission
- Botulinum toxin – vesicle release fusion proteins
- Proteins blocked by botox - paralyzes muscle b/c ACh can’t come out, no contraction
- Treatment for wrinkles and excessive sweating
- Sarin (nerve gas) – AChE inhibitor
- Blocks breakdown of ACh all over body all at once → OD of ACh → death if not treated with atropine
In Myasthenia Gravis, we want to ____ ACh
Increase by blocking AChE
In Myasthenia Gravis, there is creation of antibodies against
ACh receptors
Tyrosine is the precursor to
L-dopa, dopamine, NE, epinephrine
NE isn’t broken down in the synapse, but taken back up into the ___ by the transporter ____
Presynaptic neuron, NET
The enzyme that breaks down monoamines is
Monoamine oxidase
How do MAOIs treat depression? What is the catch?
MAOIs prevent the breakdown of NE and dopamine
Dangerous because can lead to high levels of neurotransmitters and a lot of drug interactions
What are the 7 targets for cholinergic drug action?
- Synthesis of Neurotransmitter
- Storage of Neurotransmitter
- Vesicle Secretion
- Vesicle Cycling and Endocytosis
- Reuptake of Neurotransmitter
- Biotransformation of Neurotransmitter
- MAOIs
- Neurotransmitter Receptor - Multiple
Differentiate between the 2 vesicle fusion hypotheses: when releasing neurotransmitters, why does the neuron end plate not get larger?
- Clathirin coated pit recycling - clathirin embedded in membranes reform vesicles that go back up into the neuron - recycling of vesicles - so that vesicles can be reloaded
- “Kiss-and-run” - vesicle touches membrane, opens up, and then goes back to being closed and returns to the neuron
