2.D Flashcards
Describe the division of the nervous system.
nervous system is divided into CNS and PNS
CNS is divided into brain and spinal cord
PNS is divided into sensory and motor
motor is divided into autonomic and somatic
autonomic is divided into sympathetic and parasympathetic
Define the following: neuron, nerve, ganglia, plexus, synapse
neuron: the major cell type of the nervous system, excitable cell that processes and transmits information via chemical and/or electrical signals
nerve: bundle of neuronal axons
ganglia: structure containing multiple cell bodies linked by synapses
plexus: branched network of interconnecting nerves
synapse: meeting point of two neurons
What is the role of the autonomic nervous system?
regulates autonomic functions of the body that occur without conscious control
Describe the characteristics of the autonomic nervous system.
distributed throughout the body
innervates the heart, blood vessels, glands, viscera, smooth muscle in some tissues
made up of nerves, ganglia, and plexuses
sub-divided into sympathetic and parasympathetic
What are a few things that the autonomic nervous system controls?
changes in stomach secretions
changing heart rate
redistributing blood
effecting body temperature
What are the rations of pre-ganglionic neurons to ganglionic neurons for the parasympathetic and sympathetic nervous system?
parasympathetic is 1:1
sympathetic is 1:20
What are the rations of pre-ganglionic neurons to ganglionic neurons for the parasympathetic and sympathetic nervous system?
parasympathetic is 1:1
sympathetic is 1:20
True or false: parasympathetic fibers ramify and its terminals contact large numbers of post-ganglionic neurons
false
this is describing sympathetic fibers
What are the phrases used to describe the sympathetic and parasympathetic nervous system?
sympathetic: fight or flight
parasympathetic: rest and digest
Describe the anatomy of the sympathetic nervous system.
thoracolumbar system
ganglia are located near the spinal column
pre-ganglionic axons are short
post-ganglionic axons are long
rapid coordination of multiple organ systems
What happens to the sympathetic nervous system during a moment of stress?
- signal is propagated along efferent nerves of the brain and pre-ganglionic neuron to the ganglion
- at the ganglion the pre-ganglionic neurons release ACh into synapses
- stimulates action potentials in the post-ganglionic neurons
- signal is propagated along post-ganglionic neuron to effector organ
- at the effector organ the post-ganglionic neurons release NE
Which neurotransmitters are released by the pre-ganglionic and post-ganglionic neurons of the sympathetic nervous system?
pre: acetylcholine
post: norepinephrine
What happens on a system level when the sympathetic nervous system is activated?
pupils dilate
salivary glands are inhibited
heart rate increases
breath rate increases
blood flow is directed to the heart, lungs, and skeletal muscle
blood flow is directed away from the stomach, intestines, and sex organs
piloerection
Describe the anatomy of the parasympathetic nervous system.
craniosacral system
pre-ganglionic axons are long
post-ganglionic axons are short
distributed regulation of specific organ systems
True or false: the parasympathetic nervous system is activated by the presence of relaxation
false
activated by absence of stress
What happens to the parasympathetic nervous system during the absence of stress?
- signal is propagated along efferent nerves of the brain and pre-ganglionic neuron to the ganglion
- at the ganglion the pre-ganglionic neurons release ACh into the synapse
- stimulates action potentials in the post-ganglionic neurons
- signal is propagated along post-ganglionic neuron to effector organ
- at the effector organ the post-ganglionic neurons release ACh
What happens on a system level when the parasympathetic nervous system is activated?
pupils constrict
salivary glands are activated
heart rate decreases
breath rate decreases
digestion and peristalsis increases
blood flow to the sex organs increases
Which receptors does norepinephrine act on? Describe these receptors.
alpha receptors:
-smooth muscle cells of organs & blood vessels around organs
-NE binds to alpha receptors=constrict=less blood flow
beta receptors:
-heart & blood vessels around lungs & muscle
-NE binds to beta receptors=relax=more blood flow
What is happening when ACh is released onto the adrenal glands?
the adrenal medulla releases NE and epinephrine into the bloodstream so now these molecules are hormones and they boost the sympathetic response but in a MUCH SLOWER manner
What is the difference between a hormone and neurotransmitter?
neurotransmitter: compound released into synapse
hormone: compound released into blood stream
True or false: a compound can be a neurotransmitter and hormone but it depends on the job it is completing
true
What are the key receptors of the sympathetic nervous system?
alpha and beta
What are the key receptors of the parasympathetic nervous system?
muscarinic M1-M5
nicotinic Nn-Nm
What are the key receptors of the parasympathetic nervous system?
muscarinic M1-M5
nicotinic Nn-Nm
Describe the receptors of the parasympathetic nervous system.
muscarinic receptors:
-M1-M5
-metabotropic G protein coupled receptors (GPCRs)
-work by altering Ca and K flux and altering secondary messengers like cAMP
nicotinic receptors
-Nn(neuron)-Nm(muscle)
-ionotropic ligand-gated ion channels
-increase Na, K, and Ca permeability into the cell
True or false: most PNS nerves pass through the spinal cord
false
cranial nerves go from the brain almost to the effector organ
Describe all 12 cranial nerves.
- olfactory: scents from nose to the brain (sensory)
- optic: vision from eye to brain (sensory)
- oculomotor: moves 4/6 eye muscles (motor)
- trochlear: moves eyes down (motor)
- trigeminal: face and jaw (both)
- abducens: moves eyes side to side (motor)
- facial: muscles for facial expression (both)
- auditory: info from cochlea to brain (sensory)
- glossopharyngeal: tongue and pharynx (both)
- vagus: heart, digestive tract (both)
- spinoaccessory: head and shoulder movement (motor)
- hypoglossal: swallowing reflex and speech (motor)
Where do the trigeminal, facial, glossopharyngeal, and vagus nerve relay sensory information to?
solitrary tract nucleus
Which cranial nerves pass through the solitary tract nucleus?
facial
trigeminal
glossopharyngeal
vagus
True or false: the actions of the sympathetic and parasympathetic nervous systems are agonistic
false
they are antagonistic
Describe junctional transmission.
- neurotransmitter is packed into synaptic vesicles at the axon
- transmitter crosses synaptic cleft, interacts with receptor and evokes a response from the post-synaptic neuron
- summation of responses evoked by transmitter results in a change in the post-synaptic neuron
- enzymes, reuptake pumps, or simple diffusion limit the transmitters signal
List some characteristics of receptors.
selective in their ligand binding
modifiable when ligand binds
receptor site is the location of binding
Define the following: receptor, receptor site, effector, spare receptor, agonist, antagonist, constitutive activity
receptor: molecule to which drug binds and brings change to the biological system
receptor site: specific region of the receptor where drug binds
effector: component that accomplishes the biological effect
spare receptor: receptor that does not bind agonist when drug concentration is sufficient to produce maximal effect
agonist: drug that activates its receptor
antagonist: drug that binds without activating receptor and prevents activation
constitutive activity: receptor-effector activity without agonists
How are receptors regulated?
number, location, interaction with effectors
desensitization (tachyphylaxis)
internalization (recycled)
substrate depletion
down or up-regulation
Differentiate between metabotropic receptors and ionotropic receptors.
metabotropic receptors:
-G protein coupled receptors
-slower, modulatory response
-single 7 helix subunit
-ex: mAChR
ionotropic receptors:
-ligand gated ion channels
-rapid response
-oligomeric (>1 subunit)
-ex: nAChR
Describe cholinergic transmission.
- acetylcholine synthesis: choline acetyltransferase
-ChAT transfer acetyl group from acetyl CoA onto choline - choline transport and storage: choline transporter & vesicular ACh transporter
-CHT1 brings choline into axon (ATP-dependent, rate limiting)
-VAChT bring ACh into synaptic vesicles (ATP-dependent) - release of ACh by SNAREs: VAMPs & SNAPs
-when an axon terminal depolarizes…
–>voltage gated Ca channel opens
–>allows for interaction between VAMPs and SNAPs
–>fusion occurs, allowing ACh to exit cell by exocytosis - ACh binds the receptor
- ACh degradation: acetylcholinesterase
-ACh is broken down quickly in the synaptic cleft
–>AChE hydrolyzes ACh to acetate and choline (get recycled)
What inhibits CHT1?
hemicholinium
What inhibits VACht?
vesamicol
What inhibits ACh release?
botulinum toxin
What do VAMPs and SNAPs stand for?
vesicular-associated membrane proteins
synaptosome associated proteins
How long is ACh present in the synapse or neuromuscular junction?
less than 1 millisecond
Describe nicotinic acetylcholine receptors.
5 homologous subunits form a Na-K pore
Na-K is opened by agonist
subdivided based on location and ability to bind bungarotoxin
Are fetal muscle-type nAChR the same as adult ones?
no, different subunits
transition into adult nAChR decreases ACh affinity
Where do you find neuronal-type nAChR?
peripheral ganglia, adrenal medulla, and brain
Describe Gq-coupled GPCRs.
M 1,3,5
-ACh activates Gq
-Gq activation releases calcium
-calcium release causes muscle contraction
Describe Gi-coupled GPCRs.
M 2,4
-activates K channels
-inhibits Ca channels
-blocks cAMP
=net effect of hyperpolarization
What are cholinomimetics clinically useful for?
glaucoma
loss of normal function in bowel and bladder
smoking cessation
What happens with muscarinic toxicitiy?
miosis
bronchoconstriction
excessive GI activity
sweating
vasodilation
bradycardia followed by tachycardia
What happens with nicotinic toxicity?
fasciculations and paralysis
stimulation followed by depression
addiction
What happens when we inhibit AChE?
DUMBBELSS
diarrhea
urination
miosis
bronchoconstriction
bradycardia
excitation
lacrimation
salivation
sweating
What are the catacholamines?
NE, epinephrine, dopamine
What do the actions of catecholamines have therapeutic utility for?
hypertension, mental disorders, bronchospasm
Describe catecholamine synthesis.
-tyrosine transported into cell
-tyrosine converted to DOPA by tyrosine hydroxylase
-DOPA converted to dopamine by AAADC
-dopamine transported into vesicle VMAT2
-dopamine converted to NE by dopamine hydroxylase
-NE converted to epinephrine by PNMT in chromaffin cells
What is the rate-limiting step of adrenergic transmission.
tyrosine hydroxylase
List the steps in adrenergic transmission.
catecholamine synthesis
catecholamine storage
catecholamine uptake
release of NE by SNAREs
regulation of NE release
termination of NE release
Describe catecholamine storage.
regulated by vesicular monoamine transporter 2 (VMAT2)
-pH dependent pump (exchanges 2H per catecholamine)
-catecholamines feedback on TH to prevent more production
-TH deficient humans: rigidity and hypokinesia
-dopamine hydroxylase deficient humans: orthostatic hypotension
-reserpine is a VMAT2 inhibitor
Describe catecholamine uptake.
regulated by norepinephrine transporter (NET)
-Na dependent reuptake pump
-inhibited by TCAs and cocaine
-methamphetamines inhibits or reverse
Rank the catecholamines in their affinity for NET.
dopamine>NE>epinephrine
Describe the release of NE by SNAREs.
regulated by VAMPs and SNAPs
-voltage gated Ca channels open
-Ca allows for interaction between VAMPs and SNAPs
-membrane fusion occurs, allowing NE to exit by exocytosis
What happens if we inhibit N-type Ca channels?
hypotension due to reduced NE
Describe autoreceptors in adrenergic transmission.
a receptor that is present on the same cell as the released transmitter
Which adrenergic receptors inhibit NE release? Which enhance NE release?
inhibit: a2A, a2B, a2C
enhance: B2
How much NE is recycled? Which transporter does this?
87%
NET
Which enzymes inhibit NE release?
MAO and COMT
Which adrenergic receptors are Gq-coupled GPCRs? What does their mechanism look like?
a-1A,B,D
mechanism is same to Gq-coupled receptors in cholinergic transmission
end result is contraction via Ca release
Which adrenergic receptors are Gi-coupled GPCRs? What is their mechanism/end result?
a-2A,B,C
hyperpolarization via inhibition of Ca channels and secondary messengers and activation of K channels
Which adrenergic receptors are Gs-coupled GPCRs? What is their mechanism/end result?
b-1,2,3
excitability via activation of Ca channels and secondary messengers and inhibition of K channels
Explain desensitization in regards to catecholamines.
repeated exposure of catecholamines-sensitive tissue to agonist causes a progressive diminution of response
What are the two types of nicotinic receptors? State where you would find them, their mechanism, and major functions.
Nn
-location: ANS ganglia
-mechanism: Na-K ion channel
-function: depolarize, evoke an AP
Nm
-location: neuromuscular endplate
-mechanism: Na-K ion channel
-function: depolarize, evoke an AP
What are the types of muscarinic receptors? State where you would find them, their mechanism, and major functions.
M1
-location: CNS, ANS ganglia
-mechanism: Gq-coupled
-function: depolarization of autonomic ganglia, increase gastric secretion
M2
-location: heart, CNS, smooth muscle
-mechanism: Gi-coupled
-function: hyperpolarize the heart (decrease HR), contract smooth muscle
M3
-location: smooth muscle
-mechanism: Gq-coupled
-function: contract smooth muscle,
M4
-location: CNS
-mechanism: Gi-coupled
-function: inhibit neurotransmitter release
M5
-location: CNS, substantia nigra
-mechanism: Gq-coupled
-function: dopamine release
