Cell signalling Flashcards
what percent of CNS cells are neurons
10% of CNS cells
can neurons continue devideing
No, terminaly differentiated (non-dividing)
Roll of Cell body in neurons
Protein synthesis
what part of the neuron is polarized
Dendrites and Axons
roll of dendrites
signal reception
Roll of axons
Singal transmission
what does the internal system for protein transport do
Normal metabolic function
respond to injury
route for viral infection
how much of the CNS is Glial
90%
can glial cells devide
yes
PNS glial cells
Schwann cells
roll of schwann cells
Myelination in the PNS
Glial cells in the CNS
Oligodendrocytes
Microglia
Astrocytes
roll of oligodendrocytes
myelination in the CNS
what are microglia cells like
MAcrophage-like
roll of microglia
Phagocytic
Roll of Astrocytes
REgulate extracellular fluid (remove K and neurotransmitters)
Buffering roll (homeostasis)
provide neurons metabolically
what forms the blood brain barrier
AStrocytes surrounding brain capillaries
what can lead to demyelination
Guillain-Barre syndrome
PEripheral nerve damage
Multiple Sclerosis (CNS)
what is Guillain -Barre syndrome
Autoimmune disease resulting in demyelination of peripheral motor axons
how does a neuron interact with microglia
- Microglia originally kept unreactive by neuron glycoprotein
- Neuronal injury releases intracellular ATP inducing motility (chemotaxis)
- Microglia remove damages neuronal debris
action of microglia interaction with neuron
Not well understood
Makes contact with healthy neurons
PRuning unused dendrtes
how does stuff move down the axon
Microtubules
Anterograde transport
From cell body toward terminal
motor protein for anterograde transport
Kinesins
what are Kinesins like
Myosin contractile proteins
speed of fast anterograde transport
400mm/day
speed of slow anterograde transport
.2-2.5mm/day
what does fast anterograde transport
Organelles such as neurotransmitter vesicles (Small)
what does Slow anterograde transport
structural proteins (large)
what does Retrograde transport
Dyeins
speed of retrograde trasport
fast (400mm/day)
what does Retrograde transport
Growth factors
Virus… (bad)
how is herpes simplex virus Type I transmitted
via oral contact
how many people have herpes simplex virus type I
up to 75% of in adult population
symptoms of herpes simplex virus type I
usually asymptomatics
how is the Herpes simplex virus type I transmitted in the body
retrogradely to the trigeminal ganglion
what happens to Herpes simplex virus type I during latency
TRansciptionally quiet
what can happen if an infant gets herpes simplex virus type I
goes beyond trigeminal ganglion and causes encephalitis
how can Herpes Simplex VIrus Type I be activated
By fever, sun, cold, trauma, or stress
how does Herpes Simplex Virus Type I show symptoms
TRansmitted anterogradely to peripheral tissue, lips, palate, causing painful blisters
axonal transport roll in nerve regeneration
important
can damages CNS neurons regenerate
No
what happens to a damages CNA neuron
axons sprout, but do not reach target
what prevents surviign axons of the damages CNS neurons from reaching their target
Gliosis (Scare Formation
what inhibits axon regeneration in the CNS
astrocytes making chondroitin sulfate proteoglycan
CAn PNS nerve damage be recovered
can take place depending onseverity
what helps with PNS neuron recovery
Schwann cells promote axonal regeneration
how does PNS fucntional recovery matter
nerve injury from maxillofacial surgery (Tooth extraction/dental procedures)
severe nerve injury leads to
1st: Anterograde (wallerian Degeneration)- parts distal to lesion destroyed
and terminal degeneration -destruction of synapse
2. cell death
3. transganglionic degeneration - moves up the dendrites/ axons past the cell body
4. transynaptic degeneration - death of a CNS neuron
the closer the cell injury to the ganglion
the more severe the nerve injury
less sever nerve injury leads to
terminal and anterograde degeneration
Chromatolysis
what is Chromatolysis associated with
associated with protein synthesis in an injured cell
what happens to the cell body in CHromatolysis
Cell body swell
Eccentric nucleus
action of schwann cels in regernation
Schwann cells proliferate
production of laminin for substrate for regenerating axons
Schwann cell secrete NErve growth factor (NGF)
NGF transported to ganglion cell body
roll of NGF (nerve growth factor)
regulates gene expression and promotes sprouting
- microtubules and microfilaments (structural)
- neurotransmittter prudction
- ion channel
- neurotransmitter receptors
what happens to the cell body in severe and not severe cell injurt
cell body only injured in non-severe
what does Collateral sprouting do
when the cell of a ganglion dies, other cells of that ganglion can spout branches from its dendrites/axons to take over some of the sensory action/axonal action of the dead nerve
what signals for collateral sprouting
dead neuron
NGF transported via retrograde transport
how was collateral sprouting found
ipsilateral removal of trigeminal nerve
eventually started gaining sensation past the midline
relationship between collateral sprouting and age
as you get older, you get less collateral sprouting
what does Neuronal polarity depend on
Distribution of channel types
High density of Na+ channels allong the axon support
Action Potential
High density of Ca++ channels along the axon supports
Synaptic release
what is a snyapse
Anatomically specialized junctiton between a neuron and another cell at which electrical activety of the presynaptic neuron influences the electrical activity of the post synaptic cell
typesof Synapses
Chemical
Electrical (gap junction)
size of the cleft in the chemical synapse
10-20nm
what is found in the chemcial synaptic cleft
pre-synaptic vesicle release
post-synaptic receptors
roll of electrical synapses
Fast and synchronization
commonness of electrical synapse
A few are found in the CNS but not common
types of chemcial synapses
Axon-somatic
Axodendritic
Axo-axonic
Location of receptors
Postsynaptic- on the post synaptic neuron
Presynaptic- on the axon to be acted on by a different axon
autoreceptor- on the axon to be acted on by its own neurotransmitter
roll of presynaptic receptors
mediates pre-synaptic inhibition and excitiation
types of Postsynaptic receptors
Ionotropic
Metabotropic
what are ionotropic recetpors
ion channels directly gated
what are metabotropic receptors
G-protein/2nd messenger (indirect gating
what is Synaptotagmin
Ca++ sensitive docking proteins for vesicle fusion and release
what happens where a transmitter binds to a ionotropic receptor
gates (open/closes) the pore
sped of direct gating
very rapid, msec
what happens when a transmitter bind to a Indirect gate
Activates G protein
G protein activates 2nd messenger
2nd messenger activates gate in channel
speeed of indirect gating
can be msec to hours
what happens in an excitatory synapse
influx of cations Na, Ca, K
what happens in an inhibitory synapse
Influx of anions, Cl
efflux of K
size of the post synaptic potential
about .5 mV (need more than one to reach threshold
temporal summation
adding together of Post synaptic potential from one synaptic contact over time
spacial summation
adding together of post synaptic potential produced by different synapses
what might a drug do to synaptic junction
- increase leakage of neurotransmitter to cytoplasm so its get broken down by enzymes
- increase transmitter release into cleft
- block transmitter release
- inhibit transmitter synthesis
- block transmitter reuptake
- block cleft enzymes that metabolize transmitter
- bind to receptor on postsynaptic membrane to block or mimic transmitter action
- ihibit or stimulate second-messenger activity within postsynaptic cell
function of neurotransmitter
Rapid communication (msec)
action of neurotransmitters
Acts on postsynaptic cell to produce Excitatory PSP or Inhibitory PSP
when are neuromodulators released
Co-released with neurotransmitter
action of Neuromodulators
- act postsynaptically to amplify/dampen on going synaptic activity
- act on pre-synaptic cell to alter synth, release, uptake, or metabolism of neurotransmitter
- can change protein synth or enzyme activity
speed of Neuromodulators
slow min-days
where is Acetylecholine synthesized and stored in the cell
in the synaptic terminal and stored in vesicles
what is acetylecholine synthesized from
Choline and acetyl Co-A
how is Acetylcholine action stopped
diffusion and degradation
what degrades acetylecholine
Acetylcholinesterase
what happens to choline from degraded acetylecholin
re-uptake by presynaptic neuron for re-synthesis
generally where is acetylcholine located in the nervous system
in a limited number of neurons with widespread projuctions
receptors for Acetylcholine
Nicotinic
Muscarinic
Function/disease of AcetyleCholine
Myasthenia gravis
Alzheimers disease
percise location of ACh neurons in the CNS
BAsal Forebrain
Pontine Nuclei
lower Brainstem
ACh roll in BAsal forebrain
Cognitive function
ACh roll in Pontine Nuclei
Sleep regulation
Lower brainstem Cholinergic neurons
Motor Neurons
Preganglionic sympa
preganglionic parasympa
Postganglionic Parasympa
Cholingergic motor neurons
Oromotor nuclei
preganglionic parasympa cholingeric neurons
Pre-salivary neurons in brain stem
Postganglionic parasympa cells in brain stem
Salivary cell innervation
what kind of receptor is a nicotinic receptor
Ionotropic
what does the nicotinic receptor bind to
Nicotine
where is nicotinic receptors found
In the CNS nd PNS
what happens when ACh binds to Nicotinic receptors
opens ion channel within receptor allowing Na and K to pass
what happens with Nicotinic recetpors in the neuromuscular junction
Depolarization
what blocks Nicotinic receptors
Curare
what kind of recetpor is Muscarinic recepors
Metabotropic
what does muscarinic receptors bind
Muscarine ( a point in mushrooms)
where are Msucarinic receptors found
In the CNS and PNS
parasympathetic postganglionic synapse (salivary glands)
what does Binding of ACh to Muscarinic receptors do
Triggers G protein that open or close ion channels leading to depolarization or hyperpolarization
what blocks Muscarinic receptors
Atropine
what is Myasthenia Gravis
Autoimmune disorder where individuals make antibodies to nicotinic receptors, eventually degrading them
symptoms of Myasthenia gravis
Weak Muscles
treating Myasthenia gravis
Acetylcholinisterase inhibitors
the most common form of dementia
Alzheimer’s disease
what is all involved in alzheimer’s disease
many neuronal populations
Alzheimer’s disease is caused by what
Loss of neurons in nucleus basalis, leadin gto decrease in cholinergic activity in cortex
what are biogenic amines synthesized from
Amino acids
Catecholamines
Dopamine
Norepinephrine
Epinephrine
what are Catecholamines synthesized from
Amino acid Tyrosine
where are CAtecholamines Syntheized and storeed
In presynaptic terminal and stored in vesicles
how is CAtecholamines released
Ca++ depended
how is the action of Catecholamines stoped
presynaptic neuron re-uptake
Diffusion
Degradation
what degrades CAtecholamines
Monoamine OXidase (MAO)
what does MAO inhibitors do
prolongs activity of Catecholamines
use of MAO inhibitors
therapeutic for mood disorders
how is Dopamine synthesized
L-Dopa and dopa decarboxylase in synaptic terminal
Location of Dopamine in Nervous system
Limited CNS neurons
Receptors for Dopamine
D1 and D2
what type of receptors are dopamine receptors
Indirect, G-protein coupled
function/disease of Dopamine
Motor function/dysfucntion
- parkinson’s disease
- tardive dyskinesia
Addiction
Nucleus for Dopamine
Ventral tegmental area
Substantia nigra
what is the Ventral tegmental area associated with
Reward and addicition
action of coke and amphetamine
prolong dopamine action at synapse in Tentral tegmental area
what does the substantia nigra associated with
Motor system
loss of dopamine at the substantia nigra leads to
PArkinsons’ disease
treating parkinsons
L-dopa given
action of D1
activate adenylate cyclase
action of D2
Inhibit adenylate cyclase (leading to hyperpolarization)
what do prescribed antidepressents and antiemetics bind to
Block D2 receptors
what can prescribed D2 blockers cause
Tardive Dyskinesia
how often do people get Targive Dysinesia
20-50% in patients receiving dopamine blocking drugs
what does Targive reflec
Delayed onset
is Tardive Dyskinesia more common in old
yes
symptoms of Tardive dyskinesia
PResented as rhythmic oral movements (oral-buccal-lingual stereotopy)
How is Norepinephrine synthesized
Dopamine acted on by Dopamine decarboxylase
where is NE synthesized
In the synaptic terminal
how is NE action stopped
MAO
Diffusion
re-uptake
location of NE in the nervous system
NE neuron include sympathetic postgnaglionic neurons
Some CNS neurons with lost of projections
Recptors for NE
G protein coupled receptors (alpha and BEta)
Function/disease of NE
many autonomic and homeostatic function
nucleus for NE
Locus Ceruleus
other brainstem
Affect of NE depends partly on
what receptor type it binds to
action of locus ceruleus for NE
attention/sleep
action of brainstem groups of NE
autonomic and homeostatic fucntion
action of alpha 1 NE receptor
Intracellular release Ca++ (excitation)
action of alpha 2 NE receptor
Opening K+ channels or blocking Ca++ (inhibitor
action of beta NE receptor
opens Ca++ channels
why is epinephrine combined with local anesthetics
restrict diffusion of anesthetic
what NE receptor does Smooth muscle have
Lots of Alpha 1, little beta 2
NE action on smooth muscle alpha 1 and beta 2 leads to
alpha 1: contraction
beta 2: dilation
NE action of BEta 1 of heart leads to
contraction
what is Serotonin synthesized from
typtophan
where is serotonin found
raphe nuclei in brinastem
recetpors for serotonin
G-protein coupled recetpros (16 subtypes
what serotonin synapse is the target of mood-altering drugs
5-HT
functions of serotonin
Range from sensorimotor system to cognitive function (mood)
what is Histamine derived from
Amino acid Histidine
where is Histamine found
In small population of hypothalamic neurons
what recetpors respond to Histamine
G-protein coupled
roll of Histamine
Sleep-wakefulness
How common are the neurons that synthesizecatecholamine ligands
very limited in location
where are receptors for catecholamines generally found
Throughout the CNS
What type of receptor is normal for Catecholamines
G-protein coupled with many subtypes to open and close ion channels
general function of Catecholamines
Arousal/attention, feeding, movement, cognitive function (many)
dissorders of catecholamines leads to
Motor Dysfunction: Parkinson’s, tardive dyskinesia
Cognitive disorders: depression, schizophrenia, addiction
what are the excitable amino acid neurotransmitters
Glutamate and aspartate
the most common excitatory neurotransmitter
Glutamate
what receptrors do amino acid neurotransmitters bind
Ionotropic : AMPA, Kainate, NMDA
- premeable to Na, K, and Ca++
also metabotropic receptors (G-protein)
full name for the NMDA REceptor
N-methyl-D-Asparate
what is the roll of the NMDA receptor
involved in functions that loast: memory formation, chronic pain
what type of cell death is the NMDA REceptor associated with
Excitotoxicity
what causes excitotoxicity
excessive activation (epilepsy, trauma, stroke) Intracellular Ca++ reaching toxic levels (Excited to death)
what is the synaptic mechansism of long term potentiaion
the NMDA Receptor
the most common excitatory neurotransmitter
Glutamate
are amino-acids excitatory or inhibitory
both
tetanic stimulation
rapid stimulus on pre-synaptic side
how does long term potentiation occure
there is tetanic stimulation then to the point were even one AP is strong enough to create an AP in the post synaptic cell
-synapse is changed by the NMDA receptor (long term change in the synapse)
How does NMDA mediated Potentiation occur
- High-frequency AP in presynaptic cell
- Glutamate is released
- Glutamate binds to both AMPA receptor and NMDA receptor
- AMPA lets Na in, depolarizaing the membrane by 20-30mV
- NMDA lets out Mg++ due to the depolarization and CA++ enters to activate the second messenger system
- long lasting increase in glutamate receptors and sensitivty
- long lasting increase in glutamate synth via retrograde messsenger
Depolarization via AMPA/Kainate receptors leads to what
Removal of Mg+ black (LTP_
Calcium enrey into cell via NMDA receptor leads to
Phosphorylation of NMDA receptor
Phosphorylation of AMPA receptors
INCreased AMPA
Synth of retrograde messenger NO
what does NO do for LTP
facilitates glutamate synth/release pre-synaptically
how long is LTP
variable time duration
Glutamate REuptake PAthway
Glutamate release Postsynaptic binding Uptake by astrocyte (glutamate transporter) Conversion to glutamine Glutamine release Neuronal glutamine uptake Conversion to glutamate
Inhibitory amino acid
GABA (gamm-amminobutyric acid) - main
Glycine
what is GABA made from
modified form of glutamate
receptors for GABA
GABA A
GABA B
what type of receptor if GABA A
ionotropic that opens Cl- channel
what type of receptor is GABA B
metabotropic to open K channels
disease of GABA deficit
Huntington Chorea
what is Huntington chorea
form of motor spasticity from GABA deficit
where does Glycine normally inhibit
in the spinal cord
action of Glycine
opens Cl- channels
what blocks Glycine
by strychnine
stychnine leads to
Convulsions
how are peptides form
by a peptide link between 2+ amino acids
how many peptide neurotransmitters are there
80ish
examples of PEptides neurotransmitters
endogenous opioids
Substance P
neuropeptide Y
roll of endogenous opoids
pain
roll ofsubstance P
Pain
roll of Neuropeptide Y
Feding
when are peptides released
co-released with other neurotransmitters
where are peptides synthesized
Synth in soma (must be transported)
function of peptides
neuromodulator
action length of peptides
lasts a long time
how are peptide actions terminated
Proteolysis and diffusion
how does Presynpatic modulation of opoids occur
opiods bind to a Mu opioid receptor on the presynaptic cell.
This leads to more inhibition of the postsynaptic cell
how is NO synthesized
L-arginine to NO by nitric oxide synthase
how is NO stored
Not in vesicles
how is NO transmitted
free diffusible across membranes (no synapse)
Roll of NO gas
modulates neurotransmitter release (glutamate and gaba)
plays a roll in numberous brain fucntion (LTP)
is ATP excitatory or inhibitor
Usually excitatory (taste)
how is ATP released
Usually co-released with classical neurotransmitters
how is ATP stored
not always stored in vesicles (Taste)
how is ATP released
from hemichannels (like gap channels
what creceptors does ATP act on
Family of P2 receprots
- P2X: ionotropic
- P2Y: metabotropic
