Lecture 8.2: The Autonomic Nervous System and the CVS Flashcards
What is the Role of the Sympathetic Nervous System?
The sympathetic system controls “fight-or-flight” responses
What is the Role of the Parasympathetic Nervous System?
The parasympathetic system controls “rest and digest” or “feed and breed” responses
ANS vs SNS
- Autonomic is involuntary
- Somatic is voluntary
- SNS consists of motor neurones that
stimulate skeletal muscles - ANS consists of motor neurones that
control smooth muscles, cardiac
muscles, and glands
What is a Ganglion?
- A collection of neuronal bodies found in
the voluntary and autonomic branches
of the peripheral nervous system (PNS) - Ganglia can be thought of as synaptic
relay stations between neurones
Where is the Preganglionic Neurone of the Parasympathetic found? Where is the Postganglionic Neurone of the ANS found? What Neurotransmitter is released at the postganglionic synapse?
- Preganglionic Neurone soma is usually
in the brain-stem or sacral spinal chord - Postganglionic Neurone soma is
usually in a ganglion near target organ - Acetylcholine or NO
- Rest and digest response is activated
Where is the Preganglionic Neurone of the Sympathic found? Where is the Postganglionic Neurone of the ANS found? What Neurotransmitter is released at the postganglionic synapse?
- Preganglionic Neurone soma is usually
in the spine - Postganglionic Neurone soma is in a
sympathetic ganglion located next to
the spinal chord - Norepinephrine
- Fight or flight response is activated
Where does the Sympathetic Nervous System originate?
- Thoracolumbar origin
- Preganglionic neurones arise from
segments T1 to L2 (or L3)
Sympathetic Nervous System: Where do most preganglionic neurones synapse?
- Most synapse with postganglionic
neurones in the paravertebral chain
of ganglia - Some synapse in a number of
prevertebral ganglia (coeliac, superior
mesenteric, inferior mesenteric ganglia)
Where does the Parasympathetic Nervous System originate?
- Craniosacral origin
- Preganglionic fibres travel in cranial
nerves (III, VII, IX & X) or sacral
outflow from S2-S4
Neurotransmitters and Receptors in the Sympathetic Nervous System: Preganglionic & Postganglionic Synapse
- The preganglionic neurotransmitter is
Acetylcholine - The preganglionic receptor is the
nicotinic ACh receptor - The postganglionic neurotransmitter is
noradrenaline (norepinephirine) - The postganglionic receptor is the
(nor)adrenerig receptor
Neurotransmitters and Receptors in the Parasympathetic Nervous System: Preganglionic & Postganglionic Synapse
- The preganglionic neurotransmitter is
Acetylcholine - The preganglionic receptor is the
nicotinic ACh receptor - The postganglionic neurotransmitter is
also ACh - The postganglionic receptor is the
muscarinic ACh receptors
Sympathetic innervation of the sweat
glands: Preganglionic & Postganglionic Synapse
- The preganglionic neurotransmitter is
Acetylcholine - The preganglionic receptor is the
cholinerig ACh receptor - The postganglionic neurones release
ACh - The postganglionic receptor is a
muscarinic ACh receptors
What are Vagus Nerves?
- Aka the vagal nerves
- They are the main nerves of your
parasympathetic nervous system
Parasympathetic Input to the Heart: Where do Preganglionic Fibres Synapse?
Synapse with postganglionic cells on epicardial surface or within walls of heart at SA and AV node
Parasympathetic Input to the Heart: What neurotransmitter do Postganglionic Fibres release? What receptor does this act on? What is the effect?
- Postganglionic cells release ACh
- Acts on M2-receptors
- Decrease heart rate (-ve chronotropic
effect) - Decrease AV node conduction velocity
Sympathetic Input to the Heart: Where do Postganglionic Fibres originate? What do they innervate?
- Postganglionic fibres arise from T1-T4
derived-parts of the sympathetic chain - Innervate SA node AV node and
myocardium
Sympathetic Input to the Heart: What neurotransmitter do Postganglionic Fibres release? What receptor does this act on? What is the effect?
- Release noradrenaline
- Acts on β1 adrenoceptors
- Increases heart rate (+ve chronotropic
effect) - Increases force of contraction (+ve
inotropic effect)
Effect of ANS on Pacemaker Potentials: Sympathetic
What is this effect mediated by?
- Sympathetic activity increases slope
- Sympathetic effect mediated by β1
receptors, G-protein coupled receptors
(Gs) - Increase cAMP → ligand to HCN
channel speeds up pacemaker
potential
Effect of ANS on Pacemaker Potentials: Parasympathetic
What is this effect mediated by?
- Parasympathetic activity decreases
slope of the pacemaker potential - Parasympathetic effect mediated
by M2-receptors, G-protein coupled
receptors (Gi) - Increase K+ conductance and
decrease cAMP
How does noradrenaline increase the
force of contraction? (6)
- NA acting on β1 receptors in
myocardium causes an increase in
cAMP → activates PKA - Phosphorylation of Ca2+ channels
causes increased Ca 2+ entry during
AP - Also increases Ca induced Ca release
(CICR) - Increased uptake of Ca 2+ in
sarcoplasmic reticulum - Increased sensitivity of contractile.
machinery to Ca2+ - Increased force of contraction
What type of innervation do most vessels receive? What is the exception?
- Most vessels receive sympathetic
innervation - Some specialised tissue eg erectile
tissue have parasympathetic
innervation
What type of receptors do most arteries and veins have?
- α1-adrenoceptors
What type of receptors do coronary and skeletal muscle vasculature also have?
- β2- receptors
What is Vasomotor Tone?
The end result of a complex set of interactions that control relaxation and contraction of blood vessels
What is Basal Vasomotor Tone?
- In quiescent skeletal muscle, the
resistance arteries are partially
constricted - The amount of VSM contraction
necessary to maintain this partially
constricted state is called basal
vascular or vasomotor tone
What is the Effect of decreased vasomotor tone?
- Vasodilation
What is the Effect of increased vasomotor tone?
- Vasoconstriction
What blood vessels have β2-adrenoceptors as well as α1-adrenoceptors?
- Skeletal Muscle
- Myocardium
- Liver
What type of adrenaline has a higher affinity for β2 adrenoceptors?
Circulating Adrenaline
What are the effects of activating α1- adrenoceptors on vascular smooth muscle?
- Activating α1-adrenoceptors causes
vasoconstriction - Gq –> phospholipase C activation
–>releases IP3 - Increase in [Ca2+] in from stores and
via influx of extracellular Ca2+ - Lead to contraction of smooth muscle
What are the effects of activating β2-adrenoceptors on vascular smooth muscle?
- Activating β2 adrenoceptors causes
vasodilation - Gs –> increases cAMP –> activates
PKA - Opens a type of potassium channel
- Phosphorylates and inactivates Myosin
Light Chain Kinase (MLCK necessary
for smooth muscle contraction) - Leads to relaxation of smooth muscle
What are some examples of metabolites? (4)
- Adenosine
- K+
- H+
- Increased pCO2
What effect do local increases in metabolites have?
- Local increases in metabolites have a
strong vasodilator effect - More important for ensuring adequate
perfusion of skeletal and coronary
muscle than activation of β2-receptors
What type of tissue produces more metabolites?
- Active tissue produces more
metabolites
Where are Baroreceptors found?
- Carotid Sinus
- Aortic Arch
- Nerve endings in the carotid sinus and
aortic arch are sensitive to stretch - Increased arterial pressure stretches
these receptors - These afferent nerves link to the CVS
control centre
What does the ANS control in the CVS? What does it NOT control?
- Heart Rate
- Force of contraction of heart
- Peripheral resistance of blood vessels
- The ANS does not initiate electrical
activity in heart
Where is the Cardiovascular Centre in the Brain?
- Medulla oblongata
- Located in brain stem
What does the Cardiovascular Centre in the Brain contain? (3)
- Cardioaccelerator Centre
- Cardioinhibitor Centre
- Vasomotor Centre
How are the changes in the state of the
CVS are communicated to the brain? What receptors?
- Via afferent nerves
- Baroreceptors (high pressure side of
system) - Atrial receptors (low pressure side of
system) - Alters activity of efferent nerve
Drugs acting on the ANS: Sympathomimetics
- α-adrenoceptor agonists
- β-adrenoceptor agonists
- Increases in heart rate, force of cardiac
contraction, and blood pressure
Drugs acting on the ANS: Adrenoceptor Antagonists
- Reverse the natural cardiovascular
effect - For example, if the natural activation of
the α1-adrenergic receptor leads to
vasoconstriction, an α1-adrenergic
antagonist will result in vasodilation
Drugs acting on the ANS: Cholinergics
- Muscarinic agonists and antagonists
- Reduction in heart rate, the contractile
forces of the atria and the conduction
velocity of both the sinoatrial and
atrioventricular nodes
What is Propranolol (1962)?
- The first commercially successful beta-
blocker
What is Propranolol used to Treat? (7)
- Tremors
- Angina (chest pain)
- Hypertension (high blood pressure) * Arrhythmias (heart rhythm disorders) * Other heart/circulatory conditions
- Treat/Prevent Heart Attacks * Reduce the severity and frequency of
migraine headaches
Cells in the sinoatrial node (SA node) steadily depolarise toward threshold
- Hyperpolarisation turns on a slow Na+
conductance (If – funny current) - Hyperpolarisation-activated cyclic
nucleotide gated (HCN) channels - Opening of Ca 2+ channels (T-type
then L-type)
Why do different tissues have
different receptor subtypes?
- Allows for diversity of action
- Selectivity of drug action
What do G protein-coupled receptors NOT have?
- No integral ion channel
What G-protein subtype corresponds to the a1-adrenoceptor?
Gq
What G-protein subtype corresponds to the a2-adrenoceptor?
Gi
What G-protein subtype corresponds to the β1-adrenoceptor?
Gs
What G-protein subtype corresponds to the β2-adrenoceptor?
Gs
What G-protein subtype corresponds to the M1-adrenoceptor?
Gq
What G-protein subtype corresponds to the M2-adrenoceptor?
Gi
What G-protein subtype corresponds to the M3-adrenoceptor?
Gq
Acronym for remembering G-protein subtype to corresponding adrenoreceptor (a-1,2 & β-1,2 & M-1,2,3)
KISS-KIK
qiss-qiq
Adrenoceptors and muscarinic receptors are G-protein coupled receptors; how do they work? (5)
- Agonist (ACh/NA) binds to specific.
receptor - Bound receptor activates associated
G-protein - Activated G-protein activates or
inhibits an effector enzyme - Effector enzymes generate 2nd
messenger molecules - 2nd messenger changes alter cellular
biochemistry
[Gs] G-Protein Subtype: Effector and Second Messenger
- Adenylyl cyclase (+)
- cAMP ↑
[Gi] G-Protein Subtype: Effector and Second Messenger
- Adenylyl cyclase (-) –> cAMP ↓
- K+ channel (+) –> K+ ↓
- VOCC Ca2+ channel (-) –> Ca2+ ↓
[Gq] G-Protein Subtype: Effector and Second Messenger
- Phospholipase C (+)
- DAG & IP3 → Ca2+ ↑
